bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma, bone, hip capsule and drain fluid concentrations of ampicillin and flucloxacillin during total hip replacement after intravenous bolus injection of magnapen.
Authors: Parsons RL , Beavis JP , Laurence M , David JA , Paddock GM , Trounce JR
Published: July 2012

1. A rapid intravenous bolus injection of 4.0 g Magnapen (which contains 2.0 g of ampicillin and 2.0 g of flucloxacillin) was to seven patients undergoing total hip replacement immediatly before induction of general anesthesia. Postoperatively the patients patients received 2.0 g Magnapen by intramuscular injection every 6 h for up to 72 h until removal of the wound drains. 2. The plasma, bone, hip capsule and drain fluid concentrations of ampicillin and flucloxacillin were measured by a differential small plate microbiological assay method using Sarcina lutea and a penicillinase producing Staph. aureus Russell as the test organisms. 3. The mean +/‐ s.e. mean concentrations of ampicillin after this regimen were 4222.2 +/‐ 285.0 microgram/ml (plasma), 65.6 +/‐ 1.3 microgram (g (hip capsule), 19.1 +/‐ 3.8 microgram/g (cancellous bone), and 211.1 +/‐ 65.6 microgram/g (ground up bone) respectively. 4. The mean +/‐ s.e. mean flucloxacillin concentrations after this regime were 137.2 +/‐ 28.4 microgram/ml (plasma), 61.8 +/‐ 15.0 microgram/g (hip capsule), 47.1 +/‐ 9.5 microgram/g (cancellous bone) and 139.4 +/‐ 21.8 microgram/g (ground up bone) respectively. 5. An intravenous bolus injection of Magnepen (4.0 g), given immediately before induction of general anaesthesia, provides concentrations of ampicillin and flucloxacillin in plasma, hip capsule, cancellous and ground up bone, and drain fluid that exceed the MICs of these antibiotics against Staph. aureus and E. coli. 6. The plasma, hip capsule, cancellous and ground up bone concentrations of ampicillin after this dose of Magnapen do not, however, exceed the MICs of the Gram negative anaerobes that sometimes cause postoperative wound infections in these patients.
Irradiation of human skin by short wavelength ultraviolet radiation (100–290 nm) (u.v.C): increased concentrations of arachidonic acid and prostaglandines E2 and F2alpha.
Authors: Camp RD , Greaves MW , Hensby CN , Plummer NA , Warin AP
Published: July 2012

1. Human abdominal skin was irradiated with six times the minimal erythema dose of ultraviolet C (100–290 nm) radiation. Erythema appeared at 3 h, was of moderate degree by 6 h and was maximal at 12‐ 24 h. It was reduced at 48 h and by 72 h had disappeared. 2. A suction bulla technique was used for the recovery of exudate from normal and inflamed skin at 6, 18, 24 and 48 h after irradiation. 3. Prostaglandin‐ like activity, estimated by bioassay, showed maximum increase at 18 h, when erythema was also maximum. PGF 2alpha, measured by both radioimmunoassay and by combined gas‐liquid chromatography‐gas spectrometry, followed a similar time course then fell to normal, or near normal, levels at 48 h. 4. Prostaglandin E2 and arachidonic acid concentrations, measured by gas chromatography‐mass spectrometry, were maximally raised at 18–24 h. At 48 h, when some erythema was still present, though reduced, prostaglandin E2 concentrations were still raised above control values. 5. The results provide direct evidence in support of the view that the erythma following irradiation of human skin by u.v.C involves activation of arachidonic acid metabolism. However, the relationship between the erythema and increased prostaglandin activity is not fully understood.
Catecholamine sensitivity in hyperthyroidism and hypothyroidism.
Authors: McDevitt DG , Riddell JG , Hadden DR , Montgomery DA
Published: July 2012

1. Catecholamine sensitivity in hyper‐ and hypothyroidism has been studied using a standardised isoprenaline sensitivity test. 2. Seven patients with hyperthyroidism and seven with hypothyroidism were tested both when showing evidence of thyroid dysfunction and again when euthyroid. 3. No significant differences were seen in heart rate responses to isoprenaline when patients became euthyroid compared to their response when either hyperthyroid or hypothyroid. 4. These results indicate that sensitivity to catecholamines is not altered in thyroid dysfunction and, in particular, that hypersensitivity does not occur in spontaneous hyperthyroidism.
Plasma bromocriptine levels, clinical and growth hormone responses in Parkinsonism.
Authors: Price P , Debono A , Parkes JD , Marsden CD , Rosenthaler J
Published: July 2012

1. Plasma bromocriptine levels following separate oral doses of bromocriptine 12.5, 25, 50 and 100 mg have been determined in ten subjects with parkinsonism. 2. There was considerable variation between peak plasma bromocriptine levels in individual subjects after similar doses of bromocriptine. Peak levels occurred 30–210 min after dosage (mean 102 min). Peak clinical response, peak rise in plasma growth hormone level and fall in blood pressure followed shortly after peak bromocriptine levels occurred. 3. The shape of the plasma‐time curve for bromocriptine was similar with all dosages. 4. There was no significant relationship between peak plasma bromocriptine levels, peak clinical response, peak increase in growth hormone and peak fall in blood pressure. However, the degree of improvement in the signs of parkinsonism was related to plasma bromocriptine levels was achieved. 5. Metoclopramide 60 mg pretreatment had no consistent effect upon plasma bromocriptine levels, the clinical or hormonal response.
Digoxin compliance in patients from general practice.
Authors: Johnston GD , McDevitt DG
Published: July 2012

1. Compliance with digoxin therapy has been assessed in a group of fifty patients receiving the drug in general practice but not attending hospital. 2. Compliance was estimated by comparing plasma digoxin concentrations before and after a 10 day period of measured digoxin consumption and by tablet counting. 3. Twelve patients had plasma concentrations which increased by more than 0.4 ng/ml during monitored intake and eight other patients took less than 80% of their tablets. These twenty patients were considered non‐compliant. 4. A further three patients in whom plasma digoxin levels were zero when first seen but increased substantially during the run‐in period were also adjudged non‐ compliant. 5. Non‐compliance with prescribed digoxin dosage occurred, therefore, in 46% of the patients studied.
A double‐blind comparison of the effects of hydrochlorothiazide and tienylic acid (a diuretic with uricosuric properties) in hypertension.
Authors: Gillies AH , Morgan TO
Published: July 2012

1. A double‐blind comparison of the effect of tienylic acid and hydrochlorothiazide on blood pressure was made in patients with moderate hypertension. 2. The antihypertensive effect of 500 mg tienylic acid was comparable to 100 mg hydrochlorothiazide; mean decrease in supine blood pressure after 6 weeks treatment was 20/12 mmHg with tienylic acid and 17/9 mmHg with hydrochlorothiazide. Onset of antihypertensive action was within 1 week and was associated with significant weight loss. 3. Tienylic acid caused a marked decrease in serum uric acid to a mean of 0.18 mmol/1 (n = 11, P less than 0.001), this persisted through the treatment period and returned to placebo values 1 week after treatment ceased. Some patients had uric acid crystaluria and some had post‐treatment uric acid levels higher than on placebo. 4. Tineylic acid and hydrochlorothiazide caused mild hypokalemia and alkalosis with proportional decrease in plasma chloride. 5. Blood urea and serum creatinine rose with both drugs and there was an unimportant decline in plasma sodium. 6. Tienylic acid is an effective antihypertensive agent with powerful uricosuric action and appears relatively free of side effects. Further studies are necessary to determine optimal dosage regimes and long term safety.
Potentiation of isoprenaline‐induced plasma cyclic AMP response by aminophylline in normal and asthmatic subjects.
Authors: Trembath PW , Shaw J
Published: July 2012

1 The effect of intravenous aminophylline infusion (6 mg‐1 kg in 20 min, then 0.9 mg‐1 kg‐1 h thereafter) and its interaction with inhaled isoprenaline (800 microgram ex inhaler) on plasma cyclic AMP levels was studied in five normal and five asthmatic subjects. 2 Aminophylline infusion alone did not significantly change plasma cyclic AMP levels in either group. 3 In both groups, the plasma cyclic AMP response to isoprenaline aerosol inhalation was enhanced by aminophylline, although to a lesser degree in the asthmatic subjects. 4 The results provide in vivo evidence consistent with the hypothesis that in man, therapeutic doses of aminophylline may exert their clinical effects by inhibition of cyclic AMP phosphodiesterase.
The effect on myocardial contractility of a new beta‐adrenergic receptor blocking drug, penbutolol.
Authors: Sapru RP , Sharma PL
Published: July 2012

1 The inotropic effect of penbutolol, a new beta‐adrenergic receptor blocking drug, has been compared with that of propranolol in two similar groups of six subjects each. 2 Inotropic changes were assessed from changes in myocardial contractility index [LV dp‐dt/11 T] as well as the slope of the regression line relating LV dp/dt to LVED during incremental pacing. 3 Penbutolol was found to have a significant negative inotropic effect of an order similar to that of propranolol in the respective doses studied.
Evaluation of effect of acetylsalicylic acid using electrical stimulation on the forefinger of healthy volunteers.
Authors: Seki T
Published: July 2012

1 In order to determine the optimal level of electrical stimulation, the degree of pain sensitivity produced by electrical stimulation on the volar side of terminal phalange of the right forefinger was studied in 22 male and female volunteers between the ages of 20 and 27 years. 2 A stimulation frequency of 400 Hz, width of 0.1 ms and electrical potential of 55 V was found to be optimal for study fo analgesics. 3 The effect of acetylsalicylic acid was studied in 40 healthy male volunteers between the ages of 20 and 25 years. Electrical stimulation was applied for 5 s under a single‐blind method at a frequency of 400 Hz, width of 0.1 ms and electrical potential of 25, 35 and 55 V. Placebo, 250 mg, 500 mg and 1 000 mg of acetylsalicyclic acid were administered orally under double‐blind method conditions. 4 As a result of this study, it was found that acetslsalicylic acid in a dose of 500 and 1 000 mg, was effective in relieving pain with statistically significant differences from a placebo.
The features of hepatic enzyme induction with glutethimide in man.
Authors: Jackson L , Homeida M , Roberts CJ
Published: July 2012

1 Sequential measurements of D‐glucaric acid excretion were made in six healthy volunteers before, during and after 3 weeks' daily medication with glutethimide 500 mg. 2 There was a rapid rise in D‐glucaric acid excretion within 2 days of starting medication and a rapid decline when it was stopped. 3 Antipyrine clearance and indocyanine green clearance were measured before and at the end of the 3 weeks' medication. 4 There was a 55% increase in antipyrine clearance but no change in indocyanine green clearance. 5 There was no correlation between antipyrine clearance and D‐glucaric acid excretion. 6 Glutethimide causes rapid enzyme induction in man without concomitant rise in hepatic blood flow.
Age related differences in the disposition of acetanilide.
Authors: Playfer JR , Baty JD , Lamb J , Powell C , Price‐Evans DA
Published: July 2012

1 The metabolism of fifteen elderly hospital in‐patients and fifteen young people was studied, using a gas chromatography mass spectrometer method. 2 The results suggest that there is no significant change in hepatic oxidation of acetanilide with age. 3 The concentrations of metabolites were however, significantly elevated in the older group. 4 These results illustrate the importance of the decline in renal function with age in the disposition of drugs.
Some aspects of the cardiovascular pharmacology of UK 14,275 in patients with coronary artery disease.
Authors: Jennings K , Jackson PG , Monaghan M , Jewitt DE
Published: July 2012

1. A phosphodiesterase inhibitor, UK 14,275 (Pfizer) was administered intravenously to six patients with suspected coronary artery disease under‐going diagnostic cardiac catheterisation to assess its inotropic activity. 2. Intracardiac haemodynamic measurements included pulmonary and systemic arterial pressure. Left ventricular end diastolic pressure and left ventricular dP/dtmax were also measured, in addition to cardiac output using the indocyanine green dye technique. 3. UK 14,275 resulted in a significant increase in LV dP/dtmax and cardiac output. 4. No chronotropic action was observed using this agent. 5. This agent may have potential therapeutic value in the management of cardiovascular failure associated with low cardiac output.
Monitoring digoxin therapy: III. How useful are the nomograms?
Authors: Aronson JK
Published: July 2012

1. A previously described set of guidelines for digoxin therapy has been evaluated in twenty‐four patients. 2. Six different published methods (nomograms and equations) for predicting digoxin requirements have been studied to determine their clinical usefulness in the context of the twenty‐four patients. 3. The limitations of the nomograms and equations are discussed.
Comparison of atenolol and oxprenolol in patients with angina or hypertension and co‐existent chronic airways obstruction.
Authors: Perks WH , Chatterjee SS , Croxson RS , Cruickshank JM
Published: July 2012

1 The effects of atenolol (50 mg and 100 mg) and oxprenolol (80 mg) on respiratory function were studied in ten patients with angina pectoris or hypertension complicated by chronic airways obstruction. 2 In patients with “fixed” airways obstruction, neither atenolol nor exprenolol significantly affected airways resistance. 3 In patients with “labile” airways obstruction, atenolol did not produce a significant increase in airways obstruction, whereas oxprenolol did. 4 Following isoprenaline challenge (1500 microgram by inhalation), atenolol permitted full bronchodilatation, whereas oxprenolol almost completely blocked the action of isoprenaline. 5 Partial agonist activity appears to be of less clinical importance than cardioselectivity.
Studies of cardioselectivity and partial agonist activity in beta‐ adrenoceptor blockade comparing effects on heart rate and peak expiratory flow rate during exercise.
Authors: Oh VM , Kaye CM , Warrington SJ , Taylor EA , Wadsworth J
Published: July 2012

1 The effects of beta‐adrenoceptor antagonists given in single doses by oral or intravenous routes were examined in two double‐blind controlled studies performed in healthy volunteers. Heart rate and peak expiratory flow rate (PEFR) were measured at rest and during standardized exercise. 2 Propranolol 80 mg and metoprolol 100 mg orally tended to reduce, and propranolol and metoprolol 0.2 mg/kg intravenously did reduce the physiological increase in PEFR during exercise; oxprenolol 80 mg orally and 0.2 mg/kg intravenously did not. Practolol 200 mg orally reduced this increase, but practolol 1 mg/kg intravenously did not. 3 In a third study of similar design, pindolol 0.05 mg/kg intravenously did not affect exercise‐induced increase in PEFR. 4 Heart rate during exercise was reduced to a comparable extent at different times by all the active treatments. 5 Oxprenolol and pindolol share with practolol the property of partial agonist activity, which might contribute to their apparent lack of effect on airways resistance. A further possibility is that alpha‐adrenoceptor blockade helps to maintain exercise‐induced increase in PEFR.
The metabolic effects of inhaled salbutamol.
Authors: Bateman SM , Pidgeon J , Spiro SG , Johnson AJ
Published: July 2012

1 The metabolic effects of salbutamol (5 mg) given by intermittent positive pressure breathing have been studied in eight patients with airflow obstruction. 2 No changes in plasma nonesterified fatty acids, triglyceride, glucose, insulin or cortisol were seen 1 and 4 h after administration. 3 It is concluded that inhaled salbutamol does not cause the unwanted metabolic effects reported with oral or parenteral administration, and that this is a further indication for this route of administration.
A comparison of some physiological and psychological effects of Motival (fluphenazine and nortriptyline) and diazepam in normal subjects.
Authors: Ashton H , Millman JE , Telford R , Thompson JW
Published: July 2012

1 The effects in normal subjects of a single oral dose of Motival (one tablet, containing fluphenazine 0.5 mg and nortriptyline 10 mg) on the contingent negative variation (CNV), reaction time, heart rate, blood pressure and self‐rating scales for alertness, anxiety, tension, detachment and depression were compared with those of diazepam (5 mg and 7.5 mg) and placebo or propranolol (60 mg). 2 After diazepam (5 mg: twelve subjects and 7.5 mg: seven subjects) there was a significant decrease in CNV magnitude while after Motival (twelve subjects) there was no significant alteration in CNV magnitude compared to placebo. 3 After diazepam (7.5 mg: seven subjects) there was also a fall in subjective ratings for alertness and tension; this fall was significantly greater than the changes after Motival which did not reduce subjective ratings for alterness or tension below “average” levels. Anxiety ratings did not differ significantly between the two drugs. Changes after propranolol were intermediate in all scales. 4 It is concluded that under these conditions diazepam caused central nervous system depression while Motival did not.
Effect of aluminium hydroxide and glycopyrrhonium on the absorption of ethambutol and alcohol in man.
Authors: Mattila MJ , Linnoila M , Seppala T , Koskinen R
Published: July 2012

1 The effect of aluminium hydroxide and/or of glycopyrrhonium on the absorption of a single oral 50 mg/kg dose of ethambutol (EMB) was investigated on thirteen tuberculous in‐patients and on two groups of healthy volunteers with six subjects each. The EMB concentrations in serum and 10+h urine were measured by colorimetry. 2 In order to assess gastric emptying the healthy volunteers ingested ethanol, either 0.5 g/kg in 10% solution or 0.8 g/kg in 20% solution, simultaneously with the drug, and breath alcohol levels were measured repetitively. 3 Aluminium hydroxide significantly lowered the serum EMB levels of the patients during the first 4 h after the EMB intake. No consistent effect was found in the first student experiment, whereas in the second experiment aluminium hydroxide and glycopyrrhonium, alone or in combination, clearly retarded the EMB absorption. 4 Repeated breath alcohol analysis proved unsuitable to indicate the time course of gastric emptying in these circumstances.
Standardized stress and hypertension: comparison of effect of propranolol and methyldopa.
Authors: Dunn FG , Melville DI , Jones JV , Lorimer AR , Lawrie TD
Published: July 2012

1 Using a standardized form of mental stress, 21 patients with idiopathic hypertension were investigated before and after treatment with placebo (n=8), propranolol (n=7) or methyldopa (n=6). 2 Blood pressure was satisfactorily controlled in the propranolol and methyldopa groups but only the propranolol group showed modification of the pressor response to stress testing. 3 These results suggest that propranolol may provide more uniform control of blood pressure than methyldopa in patients with essential hypertension.
Outcome of pregnancy in mothers given bromocriptine.
Authors: Griffith RW , Turkalj I , Braun P
Published: July 2012

1 Information has been obtained on the outcome of 448 completed pregnancies in mothers who had been given bromocriptine at some stage in the early weeks of pregnancy. 2 The frequencies of spontaneous abortions, twin pregnancies and malformations have been compared with those reported for 'normal' populations. 3 Based on this limited material, we conclude that the use of bromocriptine to restore fertility in hyperprolactinaemic women is not associated with an increased risk of abortion, multiple pregnancy or the occurrence of malformations in the infants.
The effects of intravenous isoxsuprine on blood viscosity in patients with occlusive peripheral arterial disease.
Authors: Di Perri T , Forconi S , Agnusdei D , Guerrini M , Pasini Laghi F
Published: July 2012

1 Blood viscosity is thought to be a major factor in disorders of the peripheral circulation. 2 Ten patients with obliterative arterial disease received an infusion of isoxsuprine of 20 micrograms kg‐1 for 30 min. The infusion was followed by a highly significant and prolonged fall in blood, plasma and serum viscosity, in haematocrit and in plasma fibrinogen concentration. Blood lipid levels were also studied: total lipids and total cholesterol did not alter; triglyceride level was significantly lowered at the end of, and after, drug infusion. 3 There was no change in blood, plasma or serum viscosity in the four patients receiving a control infusion 2 days before the infusion of isoxsuprine. 4 The relationships between lowered viscosity and increasing peripheral tissue perfusion are discussed.
Identification of hydrallazine and hydrallazine hydrazone metabolites in human body fluids and quantitative in vitro comparisons of their smooth muscle relaxant activity.
Authors: Haegele KD , McLean AJ , du Souich P , Barron K , Laquer J , McNay JL , Carrier O
Published: July 2012

1 Serum and urine from hypertensive subjects on chronic oral hydrallazine therapy were studied using gas chromatographic/mass spectrometry techniques. 2 Metabolites resulting from acetylation, hydrolysis and conjugation reactions were detected. The acetone, pyruvate and alpha‐ketoglutarate hydrazone were identified. 3 The activity of the pyruvate and alpha‐ketoglutarate hydrazones were compared with that of hydrallazine using isolated rabbit aortic strips. 4 Both hydrazones were active under in vitro conditions, producing smooth muscle relaxant effects equal to those of hydrallazine. 5 It is concluded that hydrazone metabolites will contribute to the hypotensive effects of hydrallazine therapy in proportion to their relative abundance, persistence in vascular tissues and intrinsic activity.
Bronchodilator effect of delta1‐tetrahydrocannabinol.
Authors: Hartley JP , Nogrady SG , Seaton A
Published: July 2012

1 delta1‐trans‐tetrahydrocannabinol, (delta1‐THC) produces bronchodilatation in asthmatic patients. 2 Administered in 62 microliter metered volumes containing 50–200 microgram by inhalation from an aerosol device to patients judged to be in a steady state, it increased peak expiratory flow rate (PEFR) and forced expiratory volume in 1 second (FEV1). 3 The rate of onset, magnitude, and duration of the bronchodilator effect was dose related.
Comparison of the effects of D‐(‐)‐ephedrine and L‐(+)‐pseudoephedrine on the cardiovascular and respiratory systems in man.
Authors: Drew CD , Knight GT , Hughes DT , Bush M
Published: July 2012

1 In a preliminary double‐blind trial the effects of ephedrine and pseudoephedrine on the blood pressure and heart rate of resting healthy volunteers were compared. Ephedrine 60 or 90 mg were required to raise the diastolic blood pressure above 90 mmHg, whereas 210 or 240 mg pseudoephedrine were required to produce the same effect. 2 In a second double‐blind trial, patients with reversible airways obstruction were given 60 mg ephedrine or 210 mg pseudoephedrine and the effects on forced expiratory volume in one second (FEV1) compared. Both isomers produced some bronchodilation, but the effect of pseudoephedrine was less than half that of ephedrine. 3 The reasons for these differences between the isomers are discussed and the efficacy of pseudoephedrine as a nasal decongestant pointed out and explained in relation to its effect on alpha‐adrenoceptors in the nasal blood vessels.
Quantitative determination of ergot alkaloids in biological fluids by radioimmunoassay.
Authors: Kleimola TT
Published: July 2012

1 Cross‐reactivity of ergot alkaloids with an antiserum produced against lysergic acid conjugated with human serum, albumin was utilized to develop a radioimmunoassay for ergotamine, dihydroergotamine, dihydroergotoxine, ergometrine and methylergometrine in biological fluids. The antisera showed no cross‐reactivity with simpler indole structures. 2 A procedure for extraction and concentration of alkaloids in biological fluids was developed. 3 The assay is sensitive for 1.8 ng/ml ergotamine, 1.5 ng/ml dihydroergotamine, 2.2 ng/ml dihydroergotoxine, 0.7 ng/ml ergotmetrine and 0.5 ng/ml methylergometrine. 4 The assay is sufficiently sensitive to permit the measurement of urine and plasma ergot alkaloid levels and it is suitable for determination in cases where a known ergot alkaloid is used.
Individual variation in daily dosage requirements for phenytoin sodium in patients with epilepsy.
Authors: Barot MH , Grant RH , Maheendran KK , Mawer GE , Woodcock BG
Published: July 2012

1 Ninety adult patients receiving phenytoin sodium were studied prospectively in an epileptic centre. Serum concentrations of phenytoin under steady state conditions were measured by gas liquid chromatography. When clinically indicated the daily dosage rate was adjusted by 50 mg steps until a serum concentration of 10–20 mg/l was produced. 2 Concentrations within the above range were obtained in 50 patients; the required dosage rate varied from 200–500 mg/day. Twenty‐ five clinical, biochemical and haematological attributes were recorded for each patient and tested for correlation with dosage requirement. 3 The dosage requirement correlated most strongly (r = 0.57, P less than 0.001) with body surface area. This relationship (approximately 200 mg/day per m2) accounted however for only one third of the total dosage variance. 4 Amongst 18 patients receiving simultaneous treatment with phenobarbitone, the effective plasma clearance of this drug taken in conjunction with body surface area accounted for a significantly greater proportion of the total dosage variance. Multiple regression analysis failed to reveal other, more widely applicable predictors of individual phenytoin dosage requirements.
Pharmacokinetic and concentration‐effect studies with intravenous metoclopramide.
Authors: Bateman DN , Kahn C , Mashiter K , Davies DS
Published: July 2012

1 Pharmacokinetic and concentration‐effect studies have been carried out following intravenous injection of 10 mg metoclopramide hydrochloride to seven normal male volunteers. 2 It is proposed that a two‐compartment model adequately describes the disposition of the drug which is rapidly distributed (T1/2alpha = 4.9 +/‐ 1.1 min) and eliminated (T1/2beta = 165.7 +/‐ 20.2 min). Total body plasma clearance of the drug is high (10.9 +/‐ 1.5 ml min‐1 kg‐1) and approximates to liver plasma flow. 3 Metoclopramide i.v. increases gastric emptying as measured by an ethanol absorption test (P less than 0.005). The duration of this effect is at least 3 h. 4 Ethanol given after i.v. metoclopramide administration produces significant sedation during the first hour and at 3 h (P less than 0.001). 5 The effect of metoclopramide on gastric emptying, and the degree of sedation induced by ethanol would appear to be related to plasma metoclopramide concentration. 6 Metoclopramide increases serum prolactin to 59 +/‐ 5.8 microgram/1 at 30 min after injection. There is a linear relationship (r = 0.809) between serum prolactin increase and plasma metoclopramide concentration.
Simultaneous analysis of dapsone and monoacetyldapsone employing high performance liquid chromatography: a rapid method for determination of acetylator phenotype.
Authors: Carr K , Oates JA , Nies AS , Woosley RL
Published: July 2012

1 A rapid, accurate and convenient technique for determination of acetylator phenotype of patients or subjects has not been available for routine clinical application. 2 An improved method for rapid and convenient determination of acetylator phenotype is described. 3 The plasma concentrations of dapsone (DDS) and monoacetyldapsone (MAD) were measured 3 h after a single oral 100 mg dose of dapsone using a specific and sensitive high performance liquid chromatographic assay. 4 The plasma concentration ratio of monoacetyldapsone to dapsone can accurately assess acetylator phenotype in patients or subjects. 5 The clinical applications for this method are discussed.
Prolactin responses to cimetidine.
Authors: Burland WL , Gleadle RI , Lee RM , Rowley‐Jones D , Groom GV
Published: July 2012

1 An intravenous injection of cimetidine 400 mg to four healthy male subjects resulted in high blood concentrations of cimetidine and a rapid three‐fold increase in serum prolactin. 2 This effect was prevented by pretreatment with bromocriptine. 3 No increase in prolactin followed a single oral dose of cimetidine 800 mg administered to a different group of healthy male subjects. The mean peak blood concentration of cimetidine was less than 20% of that achieved with 400 mg i.v. 4 Only isolated reports have been received of gynaecomastia or galactorrhoea occurring during cimetidine treatment. In three of seven cases studied there was associated hyperprolactinaemia. This may be an idiosyncratic response at the lower blood concentration of cimetidine associated with oral therapeutic dose regimens.
Impaired theophylline clearance in patients with cor pulmonale.
Authors: Vicuna N , McNay JL , Ludden TM , Schwertner H
Published: July 2012

1 The relationship between serum theophylline concentration and daily dose was studied in 45 patients receiving aminophylline orally and in 36 patients receiving it by constant intravenous infusion. 2 Patients were categorized as uncomplicated chronic obstructive pulmonary disease (COPD) or COPD with cor pulmonale (CP). 3 Serum theophylline concentration relative to daily theophylline dose was significantly higher in patients with COPD plus CP than in patients with COPD alone. 4 Total body clearance of theophylline estimated from data obtained during constant intravenous infusion was significantly lower in COPD plus CP than in patients with COPD alone. 5 We conclude that reduced maintenance doses of theophylline are indicated in patients with COPD when complicated with CP.
The effect of sodium 2‐mercapto‐ethane sulphonate and hypertonic saline aerosols on bronchial clearance in chronic bronchitis.
Authors: Clarke SW , Lopez‐Vidriero MT , Pavia D , Thomson ML
Published: July 2012

1 The efficacy of a mucolytic agent, 2‐mercapto‐ethane sulphonate, administered in the form of an aerosol was evaluated in a group of eleven patients with chronic bronchitis in a controlled, double‐blind, crossover study. 2 Saline aerosol isotonic (1.21M, 7.1%) to the drug was used as a placebo. 3 Approximately 1 ml drug/placebo was inhaled by the patients twice a day for 3 days and a final dose was given on the mornings of the drug/placebo trial runs. 4 There was no improvement in this group of patients in lung function or subjective well being attributable to the drug. 5 The viscosity of sputum, dry macromolecular weight and N‐acetyl neuraminic acid/fucose ratio remained unaltered throughout the study. 6 An enhancement of tracheobronchial clearance was obtained following the administration of either placebo (31%) or drug aerosols (24%) Statistical significance (P less than 0.01) was only achieved for the placebo and was attributed to an increase in sputum volume.
Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide.
Authors: Whiting B , Lawrence JR , Skellern GG , Meier J
Published: July 2012

1. The metabolism and plasma kinetics of chlordiazepoxide have been determined in a group of volunteers and in a group of patients with acute alcohol intoxication. 2. Using the SAAM 26 non‐linear least squares fitting programme, all chlordiazepoxide plasma concentration v time data following oral administration could be analysed in terms of a one‐compartment open model with metabolic conversion of chlordiazepoxide to desmethylchlordiazepoxide. 3. Acutely intoxicated patients showed a prolonged elimination of chlordiazepoxide and a reduced clearance when compared with alcohol‐free volunteers. The elimination of desmethylchlordiazepoxide, on the other hand, appeared to be faster in the alcoholics. 4. Alcohol exerts significant effects on the metabolism of chlordiazepoxide in acutely intoxicated patients.
Bioavailability of chlorpropamide.
Authors: Evans M , Glass RC , Mitchard M , Munday BM , Yates R
Published: July 2012

1. The serum profiles of chlorpropamide obtained following single doses of two tablet preparations and from a suspension formulation have been compared in healthy volunteers. The amounts of chlorpropamide absorbed from the three formulations were similar but the drug was absorbed more rapidly from the suspension than from either tablet formulation. There was a small but therapeutically insignificant difference in the rate of absorption of the drug from the two tablets. 2. Changes in blood glucose concentrations were found to be related to the drug serum profile characteristics of the formulations.
Treatment of severe 2,4‐D and mecoprop intoxication with alkaline diuresis.
Authors: Prescott LF , Park J , Darrien I
Published: July 2012

1 Self‐poisoning with a selective weedkiller containing 2,4‐D and mecoprop in a 39 year old man resulted in prolonged deep coma, pyrexia, hyperventilation, hypoxaemia, myotonia, skeletal muscle damage and electrocardiographic changes consistent with cardiomyopathy. 2 The admission plasma concentrations of 2,4‐D and mecoprop were 400 and 751 microgram/ml respectively. The patient remained gravely ill with no signs of improvement for 2 days with supportive therapy and there was no fall in the 2,4‐D level. 3 Alkaline diuresis greatly increased the renal clearance of 2,4‐D, and there was a rapid fall in plasma concentration (T1/2 3.7 h) with corresponding clinical improvement. The effect on the elimination of mecoprop was similar, but less dramatic. 4 Forced alkaline diuresis may improve the otherwise very poor prognosis in severe intoxication with 2,4‐D and related weedkillers.
Pharmacokinetics and pharmacological effects of neostigmine in man.
Authors: Calvey TN , Wareing M , Williams NE , Chan K
Published: July 2012

1 The pharmacokinetics of neostigmine was studied in six patients during the reversal of neuromuscular block induced by tubocurarine chloride. The effect of the drug on neuromuscular function was simultaneously assessed by electromyography. 2 Neostigmine was rapidly eliminated from plasma after intravenous administration. The decline in the plasma concentration of the drug was invariably resolved into two exponential components. The fast disposition (distribution) half‐life of the drug was invariably less than 1 min; the slow disposition (elimination) half‐life ranged from 15.4–31.7 min. 3 Neostigmine usually increased the amplitude of the compound muscle action potential and diminished electromyographic decrement within 2 min of intravenous injection. The pharmacological effect of neostigmine was usually maximal between 7 and 15 min. There was an inverse relationship between the plasma concentration of the drug and the facilitation of neuromuscular transmission. 4 Red cell acetylcholinesterase activity was almost completely inhibited within 2–3 min of intravenous injection of neostigmine. Enzyme activity recovered to approximately 28% of control values by 30 min and to 55% by 60 min.
Measurement of activity of 5‐HT antagonists following oral administration in man: a comparison of methysergide and BW501.
Authors: O'Grady J , Peringer E , John G
Published: July 2012

1 Oral doses of BW501 and methysergide administered to healthy volunteers inhibited the ex vivo platelet aggregation response to 5‐ hydroxytryptamine (5‐HT). 2 Two volunteers received 100 mg BW501 and two received 10 mg BW501 and aggregation response was measured immediately pre drug and at 1,3 and 24 h post drug. After 100 mg BW501 the response to 5‐HT was completely inhibited at all times studied, after 10 BW501 a response too small to measure was apparent at 24 h only. 3 In two randomised crossover studies subjects received either 2 mg BW501 (nine subjects), 2 mg methysergide (six subjects) or no drug (nine subjects) and aggregation response to 5‐HT was measured immediately pre drug and at 1, 2, 3, 5, 7, 24 h post drug. 4 Methysergide (2 mg) produced complete inhibition of aggregation for 24 h after dosing; following 2 mg BW501 the aggregation response was significantly lower than on the control occasion at 1 (P less than 0.01), 2 (P less than 0.01) and 3 (P less than 0.05) h post drug. The response was inhibited by rr%, 31% and 16% at these times respectively. 5 It is suggested that this technique provides a suitable method for demonstration of activity of 5‐HT antagonists after oral dosing in man.
Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs.
Authors: Perucca E , Richens A
Published: July 2012

1 The serum concentration profile of paracetamol has been determined after administration of single 1000 mg intravenous and oral doses in six normal subjects and six epileptic patients on chronic antiepileptic drug therapy. The urinary excretion of free and conjugated paracetamol has also been determined. 2 Following intravenous administration, serum paracetamol concentration declined with first‐order kinetics. Both elimination rate and total body clearance were higher in the epileptic patients, although in neither case was the difference statistically significant. 3 The oral bioavailability (mean +/‐ s.e. mean) was significantly lower in the epileptic patients than in the normal subjects (0.77 +/‐ 0.03 and 0.89 +/‐ 0.02 respectively, P less than 0.01), whereas the urinary excretion total (free+conjugated) paracetamol was almost identical in the two groups. 4 It is suggested that the lower bioavailability of paracetamol in the epileptic patients results from enhancement of first‐pass metabolism, secondary to enzyme induction.
Pupil responses to intravenous heroin (diamorphine) in dependent and non‐dependent humans.
Authors: Tress KH , El‐Sobky AA
Published: July 2012

1. Intravenous heroin was administered to volunteers, in doses of 2.5 and 5 mg to non‐dependent subjects and does of 1/6, 1/3 and 1/2 of their prescribed daily does of opiates to dependent subjects, and pupillary responses measured before and three times during the 2 h after injection. 2. Tolerance to the miotic effects of heroin in the dependent subjects was demonstrated‐larger doses of heroin were needed to produce the same pupil response in dependent subjects than in non‐ dependent subjects and the duration of action was shorter in the former group. 3. The effect of concurrent oral methadone medication on pupil response to heroin was demonstrated. Subjects prescribed both methadone and heroin showed smaller control pupil diameters and a reduced dose effect to heroin than did subjects prescribed heroin alone.
Pindolol pharmacokinetics in relation to time course of inhibition of exercise tachycardia.
Authors: Jennings GL , Bobik A , Fagan ET , Korner PI
Published: July 2012

1 Pharmacokinetics of pindolol were studied in normal subjects given 5, 10 and 20 mg orally and 3 mg i.v. Plasma half time was 2.9 +/‐ 0.3 (s.e. mean) h for both routes; peak drug levels occurred 1–2 h after ingestion and bioavailability was 53%. Plasma protein binding was 38% and was independent of plasma concentration; the drug was not concentrated in the red cell. 2 Work‐heart rate regression lines were calculated from resting heart rate and three grades of 'steady‐state' exercise standardized for the maximum work capacity (Wmax) of each subject. The equation was characterized by slope and HR50 (calculated heart rate at 0.5 Wmax). 3 After giving 5 mg i.v. pindolol to produce maximum cardiac beta‐adrenoceptor blockade there were differences in inhibition of resting heart rate, slope, HR50 and maximum heart rate suggesting differences in sympathetic components. However, estimates of the degree of inhibition were closely similar for each variable when determined before and after atropinization indicating that the accuracy of estimation was independent of the level of vagal activity. 4 After oral pindolol peak inhibition of resting heart rate, slope and HR50 coincided with peak plasma concentration. Peak reduction of resting heart rate was greatest at the lowest dose, but inhibition of slope and HR50 were similar at all doses. 5 The different heart rate parameters recovered at different rates. After 24 h slope had returned to control, and the residual inhibition of HR50 reflected residual beta‐ adrenoceptor blockade of resting heart rate, as demonstrated by a shift in isoprenaline‐heart rate relationship. 6 Inhibition of HR50 and other exercise parameters were 20% less in the concentration range 5–20 ng/ml than peak inhibition obtained in the range 21–160 ng/ml. The higher potency of pindolol compared with propranolol can be accounted for by the difference in protein binding.
Uricosuric properties of diflunisal in man.
Authors: Dresse A , Fischer P , Gerard MA , Tempero KF , Meisinger MA , Bolognese JA , Verhaest L
Published: July 2012

1 The uricosuric effect of diflunisal was studied in eleven normal subjects. 2 Urine and serum uric acid levels were measured and used to assess the effect. 3 Diflunisal caused statistically significant decreases in serum uric acid levels and increases in uric acid clearance at 250 and 375 mg twice daily. 4 Diflunisal taken on an empty stomach caused epigastric discomfort in the high dose group which was obviated when the drug was taken with meals. 5 Diflunisal caused no abnormalities in the measured haematological, urological or biochemical parameters.
Study of urinary excretion of butobarbitone in man in relation to the percentage of ideal body weight.
Authors: Cheymol G , Bernheim C , Besson J , Dry J , Portet R
Published: July 2012

1 Thirty‐three patients with no evidence of endocrine disease, hepatic or renal insufficiency or sleep disorders, were classified in groups 1 to 4 in order of increasing of percentage of ideal body weight (IBW) respectively: less than 90% of IBW, 90–120%, 120–180%, and greater than 180% of IBW. After oral administration of 200 mg butobarbitone, concentration of the intact drug was measured by gas liquid chromatographic assay in urine samples collected during 72 h and at three times in blood. 2 A highly significant negative relationship was found between the cumulative excretion of butobarbitone with urine and the logarithm of the percentage of IBW. In contrast for a given weight, excretion of the drug with urine was found to be weakly correlated with the diuresis. 3 The cumulative urinary elimination of butobarbitone was significantly different between the groups studied, except of the difference between the group 2 and 3 of the patients. No significant difference was found between the renal clearances of butobarbitone in the four groups of subjects. 4 We conclude that redistribution of butobarbitone into adipose tissues can explain the obtained results and that obesity modifies the pharmacokinetics of the drug.
Kinetics of fluphenazine after fluphenazine dihydrochloride, enanthate and decanoate administration to man.
Authors: Curry SH , Whelpton R , de Schepper PJ , Vranckx S , Schiff AA
Published: July 2012

1 Fluphenazine (1,2‐ethanol 14C) was administered to seven human subjects as the dihydrochloride and as the enanthate and decanoate esters. 2 The subjects had previously been treated with fluphenazine injections for at least 6 months. 3 Fluphenazine was separated from its radioactive metabolites by selective solvent extraction. Plasma concentrations were measured for up to 21 days after dosing. 4 The preparations showed differences in peak concentrations, times of the peaks and half‐times of the elimination phase. The longest half‐times occurred with the decanoate and the shortest with the dihydrochloride. 5 It is postulated that the differences in kinetics relate principally to the release of the compound from the site of injection. 6 There was no evidence for presence of the esters in plasma, urine or faeces.
Plasma cinnarizine levels resulting from oral administration as capsule or tablet formulation investigated by gas‐liquid chromatography.
Authors: Morrison PJ , Bradbrook ID , Rogers HJ
Published: July 2012

1 A gas chromatographic assay for the estimation of therapeutic concentrations of cinnarizine in plasma is described. 2 Cinnarizine (75 mg) was administered orally to twelve healthy subjects in the form of capsules and tablets on two separate occasions. No difference was found in the plasma levels or absorption of cinnarizine from these formulations. 3 The mean plasma elimination half‐life of cinnarizine was 3.24 h.
Atenolol and chlorthalidone in combination for hypertension.
Authors: Bateman DN , Dean CR , Mucklow JC , Bulpitt CJ , Dollery CT
Published: July 2012

1 The hypotensive effect of single daily dosing with atenolol 100 mg and chlorthalidone 25 mg given alone or in combination has been assessed in a double‐blind, crossover, placebo controlled trial in fifteen hypertensive patients. 2 Average lying blood pressures were: Placebo 155.4/103.9 mm Hg, atenolol 134.6/85.8 mm Hg, chlorthalidone 139.5/90.1 mm Hg, combination 127.7/82.5 mm Hg. 3 The effect of the combination therapy in reducing lying diastolic pressure compared with placebo (a fall of 21.4 mm Hg) was significantly less than the 31.9 mm Hg fall predicted from the sum of the individual effects (P = 0.01). 4 Observations on blood pressure at rest and under mental, isometric and bicycle ergometer stress were made pre‐dose and post‐dose for a 12 h period at the end of the last treatment period. 5 Lying blood pressure declined from the zero hour (pre‐dose) reading on all treatments to a low at 15.00–18.00 h and then rose again. 6 The rise in systolic blood pressure after isometric exercise and mental stress was of a similar magnitude with all four treatment regimes. 7 Atenolol, alone and in combination with chlorthalidone, reduced the blood pressure and the pulse rate increase on exercise 2 h post‐dose when compared with readings 24 h post‐dose. 8 Once daily dosing with a combination of atenolol and chlorthalidone produced a fall in supine blood pressure over a 24 h period but the effect on exercise induced changes was not uniform over this period.
Cardiovascular effects of prenalterol (H133/22) in normal man.
Authors: Scott DH , Arthur GR , Boyes RN , Scott DB
Published: July 2012

1 Prenalterol, (S‐(‐)‐1‐(4 hydroxyphenoxy)‐3‐isopropylaminopropanol‐2 hydrochloride) a cardio‐selective beta‐adrenergic receptor agonist, was infused intravenously into six normal male volunteers to determine the cardiovascular effects of this drug. 2 On different occasions, each volunteer received a placebo infusion, an infusion of 0.5 mg prenalterol and an infusion of 1 mg prenalterol. Cardiac output (impedance cardiography), arterial pressure (sphygmomanometry), heart rate and ECG were measured throughout. 3 Prenalterol produced a statistically significant increase in cardiac output and at the end of the infusion this increase was 24% with 0.5 mg and 29% with 1 mg, mainly due to an increase in stroke volume (18% and 17%) with a lesser change in heart rate (+2 and +7 beats/min). Pulse pressure increased but mean arterial pressure showed little change. Peripheral resistance fell by 18% and 20%. As indicated by systolic time indices myocardial contractility increased. 4 Prenalterol at plasma concentrations in excess of 20 nmol l‐1 produced significant inotropic effects but did not markedly increase heart rate at concentrations of 60 nmol l‐1.