bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethanol oxidizing enzyme activites in liver disease.
Authors: Dow J , Krasner N , Goldberg A
Published: July 2012

1 The activites of hepatic alcohol dehydrogenase, catalase and the reduced nicotinamide adenine dinucleotide phosphate (NADPH) dependent ethanol oxidizing system were determined in liver biopsies from nine patients with liver disease and seven control subjects with non evidence of liver disease. 2 Alcohol dehydrogenase and catalase activites were significantly lower in the patients with liver disease. 3 The activity of the NADPH dependent ethanol oxidizing system was significantly greater in the patients with liver disease, when its activity was expressed in terms of mg protein or g wet weight liver. 4 It is suggested that the greater activity of the NADPH dependent system may compensate for the low alcohol dehydrogenase activites found in patients with liver disease and maintain normal rates of ethanol metabolism.
The pharmacodynamics of single doses of prorenoate potasssium and spironolactone in fludrocortisone treated normal subjects.
Authors: Ramsay LE , Shelton JR , Tidd MJ
Published: July 2012

1 The pharmacodynamic profile of single oral doses of prorenoate potassium (40 mg) and spironolactone (100 mg), as judged by reversal of the effects of fludrocostisone on the urinary electrolyte composition, was compared to that of placebo in a double‐blind crossover study in six healthy subjects. 2 Both drugs showed evidence of significant activity in all periods between 2‐16 h after treatment, and the time course of their activity was very similar. 3 In the total 24 h period after treatment both drugs significantly increased sodium excretion, the Na/K ratio and the log 10 Na/K ratio over placebo values, and urine potassium concentration was significantly reduced. Changes in urine volume and in potassium excretion were not significant. 4 The responses to prorenoate potassium (40 mg) were not significantly different from those to spironolactone 100 mg), and were very similar as judged by the urine log 10 Na/K ratio, indicating that the two drugs were approximately equiactive at these doses. 5 Reductions in urinary potassium excretion, when expressed in relation to the amount of sodium excreted, were significantly larger after prorenoate potassium than after spironolactone, confirming a qualitative difference in the pharmacological activity of the two drugs which has been reported previously.
Distribution and removal of human serum albumin‐technetium 99m instilled intranasally.
Authors: Aoki FY , Crowley JC
Published: July 2012

The efficacy of antiviral drugs and vaccines administered intranasally may depend upon the technique of application. The distribution and time‐ course of removal of human serum albumin‐technetium 99m (HSA‐Tc 99m)‐ instilled intranasally were studied in eleven healthy volunteers using a gamma camera and an anterior sodium iodide scintillation detector. In 100 randomized studies material was delivered as drops in the supine position or as a spray to seated subjects. A significantly higher proportion of ‘good’ distributions (62 in 73 tests) was obtained with drops compared with spray (1 in 27). The volume administered was varied between 0.10 ml and 0.75 ml and the concentration of HSA was changed from 3 to 30% with no significant effect upon the distribution of time‐ course of removal; pertechnetate in isotonic saline was distributed and removed in a manner comparable to HSA‐Tc 99m. Activity recorded by the detector showed an initial rapid fall associated with removal of most of the material from the nasal cavity, followed by a slower decline associated with the removal of material mainly from the anterior region of the nose. A multidose study confirmed that frequent administration by drops is required to maintain a high level of activity in the nasal cavity. Using this technique it should be possible to correlate measurements of antiviral efficacy and vaccines take‐rates with certain characteristics of intranasal applicators; such studies may lead to the design of better devices.
Serum and lung tissue levels of cephradine in thoracic surgery.
Authors: Kiss IJ , Farago E , Pinter J
Published: July 2012

Serum and lung tissue levels in fifteen patients who underwent thoracic surgery were determined by the agar‐diffusion plate method after i.m. administration of cephradine (500 mg). The mean value of the serum level 30 to 120 min after administration was 6.5 mug/ml, the mean lung tissue level was 2.6 mug/g. The lung tissue levels reached 40% of the simultaneous serum level. Four patients received cephradine for the treatment of post‐operative chest infections. This antibiotic has an important therapeutic role in cases of thoracic‐surgical infections.
Serum concentrations and bioavailability of rifampicin and isoniazid in combination.
Authors: Garnham JC , Taylor T , Turner P , Chasseaud LF
Published: July 2012

The bioavailability of rifampicin and isoniazid from formulations containing these drugs in combination has been compared to that from formulations containing either drug alone. No formulation‐related differences in either rates or extent of bioavailability were found after administration of each formulation. Mean peak serum concentrations of rifampicin (8.2‐11.7 mug/ml) occurring 2 to 4 h after doses of 600 mg, and isoniazid (3.6‐4.8 mug/ml) occurring 0.5 to 1 h after doses of 300 mg, were similar to those reported in the literature.
The relationship between liver volume, antipyrine clearance and indocyanine green clearance before and after phenobarbitone administration in man.
Authors: Roberts CJ , Jackson L , Halliwell M , Branch RA
Published: July 2012

Liver volume and the clearances of antipyrine and indocyanine green have been measured before and after administration of phenobarbitone (180 mg/day) for 3 weeks to ten healthy subjects. The measurement of liver volume by an ultrasound scanning technique yielded reproducible results which were consistent with predictions of liver size by allometric methods. Before phenobarbitone, antipyrine clearance correlated with liver volume, but there was no correlation between indocyanine green clearance and liver volume. Phenobarbitone administration increased the clearance of antipyrine significantly by 90 +/‐ 14% but there was no significant change in indocyanine green clearance or liver volume. After phenobarbitone the correlation between antipyrine clearance and liver volume persisted. There was no correlation between indocyanine green clearance and liver volume. These results suggest that in non‐medicated subjects some of the difference in antipyrine clearance is due to difference in functional hepatic parenchymal mass and that phenobarbitone increases the drug metabolising capacity per unit of hepatic mass but not total liver size.
The ralationship between changes in 5‐HT induced platelet aggregation and clinical state in patients treated with fluphenazine.
Authors: Orr MW , Boullin DJ
Published: July 2012

Platelet aggregation responses to 5‐HT and adenosine diphosphate were examined in a population of eighteen patients treated with fluphenazine decanoate for longer than one year. 5‐HT induced aggregation was enhanced in ten subjects. This enhancement was similar to that previously described in patients receiving chlorpromazine. Patients who showed enhanced 5‐HT induced aggregation showed less rateable psychopathology and less extrapyramidal side‐effects than patients who did not show enhancement. These findings suggest that platelet aggregation responses could be used to identify patients who could be safely withdrawn from long‐term neuroleptic therapy.
Acetylator phenotyping of tuberculosis patients using matrix isoniazid or sulphadimidine and its prognostic significance for treatment with several intermittent isoniazid‐containing regimens.
Authors: Ellard GA , Gammon PT
Published: July 2012

1. The acetylator phenotype of over 600 pulmonary tuberculosis patients treated with intermittent isoniazid‐containing regimens in two controlled clinical trials was determined using either sulphadimidine or a slow‐release isoniazid formulation. 2. Both methods unequivocally classified over 99% of the patients as being either slow or rapid acetylators. 3. Rapid and slow acetylation did not differ in their ability of hydrolyse acetylisoniazid to isonicotonic acid plus monoacetylhydrazine, or to conjugate isonicotinic acid with glycine. 4. Rapid acetylators acetylated the monoacetylhydrazine liberated in vivo more rapidly than slow acetylators, demonstrating that this compound is also polymorphologically acetylated in man. 5. The acetylator phenotype of the patients was without prognostic significance when they were treated on a twice‐weekly basis with isoniazid plus streptomycin plus pyraziniamide, or with isoniazid plus rifampicin. However, when patients were treated once every week for 12 months with isoniazid plus rifampicin, 5% of the rapid acetylators had an unsatisfactory response as contrasted to the complete success of the treatment in the slow acetylators.
Comparison of the effects of labetalol and propranolol in healthy men at rest and during exercise.
Authors: Richards DA , Woodings EP , Maconochie JG
Published: July 2012

1. Oral labeltalol and propranolol have been compared in healthy men with regard to the effects on heart rate, blood pressure and peak expiratory flow rate (PEFR) at rest and the changes induced by exercise. 2. Labetalol caused a dose‐related reduction in standing diastolic pressure at rest whereas propranolol did not but neither drug altered standing systolic pressure at rest. 3. In the doses compared, propranolol was consistently more potent than labetalol in influencing blood pressure changes induced by exercise, in lowering heart rate at rest and reducing PEFR at rest. 4. Labetalol and propranolol are both beta‐adrenoreceptor antagonists and the observed differences in the profiles of the two drugs are probably directly related to the additional alpha‐adrenoreceptor blocking property of labetalol not possessed by propranolol. Because of these differences labetalol may be expected to have advantages in the treatment of hypertension.
Acute haemodynamic effects of metoprolol in hypertensive patients.
Authors: Sannerstedt R , Wasir H
Published: July 2012

1. The acute haemodynamic effects of metoprolol (0.15 mg/kg body weight) intravenously were studied at rest and during exercise, in a recumbent position in five patients with arterial hypertension of WHO Stage 1 or 2. 2. Significant decreases in heart rate, cardiac output and arterial blood pressures, both at rest and during exercise, were seen. There were no changes in the calculated stroke volume or systemic vascular resistance. 3. The apparent absence of any relative preponderance of the alpha‐adrenoreceptors after acute beta‐ adrenoreceptor blockade with metoprolol warrants further studies on metoprolol in arterial hypertension.
Effects of (+) and (‐)‐propranolol on the responses of the human isolated basilar artery to cerebrospinal fluid obtained from patients with subarachnoid haemorrhage and cerebral arterial spasm.
Authors: Boullin DJ , Mohan J
Published: July 2012

1. The human isolated basilar artery has been used as a model to investigate the aetiology of cerebral arterial spasm associated with rupture of intracranial aneurysms. 2. The isolated artery is contracted by 5‐hydroxytryptamine, noradrenaline, six prostaglandins and cerebrospinal fluid from patients with ruptured aneurysms and cerebral arterial spasm. 3. These contractions are reversed by (+/‐)‐, (+)‐ and (‐)‐propranolol in concentrations known to produce local anaesthetic effects on isolated frog sciatic nerve; the (+) isomer was 2.5 to 10 times more potent (‐)‐propranolol in antagonising all contractions. 4. As the two isomers are known to have similar local anaesthetic potency but (‐)‐propranolol has greater beta‐adrenoreceptor blocking effects we conclude that the antagonistic effects described do not involve beta‐adrenoreceptor blockade. 5. The data indicate that propranolol may be of clinical use in reversing cerebral arterial spasm.
Fate of [14C]‐bumetanide in man.
Authors: Pentikainen PJ , Penttila A , Neuvonen PJ , Gothoni G
Published: July 2012

1. The fate of bumetanide was studied in four healthy volunteers both after intravenous oral administration of [14C]‐bumetanide (0.5 mg). 2. The absorption of oral [14C]‐bumetanide was rapid (absorption half‐life 0.61 h) and complete with a urinary recovery of about 80% of the intravenous or oral dose during 48 h. 3. The elimination of [14C]‐ bumetanide was rapid with a half‐life of elimination (T 1/2 beta) of 1.5 h. 4. Protein bound fraction of [14C]‐bumetanide in plasma was 95%. No bumetanide was found in red blood cells. 5. Four metabolites of [14C]‐bumetanide were found in urine. Together they accounted for about one third of the radio‐activity excreted into urine during the first 6 h after the administration of the drug. 6. Bumetanide is rapidly and completely absorbed from the gastrointestinal tract, bound extensively to plasma proteins, metabolized to some extent and excreted rapidly, principally into urine.
Ethical review in the pharmaceutical industry.
Authors: Ramsay LE , Tidd MJ , Butler JK , Venning GR
Published: July 2012

1. There seems no reason why clinical pharmacology studies conducted within the pharmaceutical industry should be exempt from the requirement of ethical review, and independent review in this situation reduces the vulnerability of the company and its employees, in addition to serving its primary function of protecting the volunteer subjects. 2. Experience within one company has shown that independent ethical review need not seriously influence the pace of research. 3. It is important that such committees should be seen to be independent and competent.
The effect of carbidopa administration on urinary sodium excretion in man. Is dopamine an intrarenal natriuretic hormone?
Authors: Ball SG , Lee MR
Published: July 2012

1 Carbidopa, a known inhibitor of the peripheral conversion of dopa to dopamine, was given to six normal volunteers to examine the effect of interference with dopamine synthesis on urinary sodium excretion. 2 On the first day of administration, carbidopa caused a significant fall not only in urinary dopamine excretion (P less than 0.01) but also in urinary sodium excretion (P less than 0.05). 3 A highly significant correlation was also found between mean sodium excretion and mean dopamine excretion in the days prior to and during carbidopa administration (r = 0.617, P less than 0.001; 4 = 0.764, P less than 0.001 respectively). 4 The significance of these findings is discussed and it is proposed that dopamine may be an important intrarenal natriuretic hormone.
The effect of dipyridamole on platelet function: correlation with blood levels in man.
Authors: Rajah SM , Crow MJ , Penny AF , Ahmad R , Watson DA
Published: July 2012

1 The effect on platelet functions of dipyridamole (a pyrimido‐ pyrimidine compound) was compared with a control group of patients taking warfarin. 2 Adhesion, aggregation and platelet factor 4 availability showed a significant decrease in the dypyridamole group. 3 Aggregation and platelet factor 4 showed a significant correlation with blood dipyridamole level. 4 Adhesion, aggregation and platelet factor 4 were reduced below the lower limit of normal at blood dipyridamole levels above 3.5 micronmol/1.
Effects of labetalol and propranolol on histamine‐induced bronchoconstriction in normal subjects.
Authors: Maconochie JG , Woodings EP , Richards DA
Published: July 2012

1 The effects of oral propranolol (80 mg), labetalol (400 mg) and placebo on blood pressure, pulse rate and FEV1 at rest and after inhaled histamine, have been compared in six healthy male volunteers. 2 At 90 and 120 min after ingestion propranolol reduced the pulse rate and labetalol reduced the blood pressure, thus confirming absorption of each drug. 3 At 120 min propranolol reduced resting FEV1 and enhanced the fall in FEV1 after histamine, whereas the alterations in FEV1 after labetalol did not differ from placebo. 4 These findings suggest that labetalol is less likely than propranolol to cause bronchoconstriction in asthmatic patients.
Measurement of thioridazine in blood and urine.
Authors: Ng CH , Crammer JL
Published: July 2012

1 Thioridazine can be specifically, simply, and reliably measured in plasma and urine by gas chromatography using hexane extraction and prochlorperazine as internal standard; fluorimetry is non‐specific. 2 The method can also measure thioridazine ring sulphoxide, and mesoridazine‐plus‐sulphoridazine (M/S). 3 After single doses plasma sometimes shows M/S in addition to thioridazine itself; it always does so on continued treatment. There is great individual variation in both components, and evidence of changes in metabolism during the early weeks. 4 Urinary excretion may be influenced by pH, but between pH 6.0‐ 7.0 about 1% of the daily dose appears in 24 h urine as the following: free thioridazine in microng quantities, M/S and ring sulphoxide each in mg amounts. 5 Patients attain steady state conditions, although plasma levels rise considerably after each dose and settle again in about 10 h. After chronic treatment is stopped to half‐life is at about 30 h. 6 Plasma levels cannot be related to therapeutic response when this is slow, as in schizophrenia, but interpretations are complicated by the production of clinically active metabolites, and by plasma protein binding.
The comparability of dosage regimens of Lanoxin tablets and Lanoxicaps.
Authors: Johnson BF , Smith G , French J
Published: July 2012

1 Twice daily administration of 0.25 mg digoxin tablets (Lanoxin) or of 0.2 mg digoxin in solution in soft gelatin capsules (Lanoxicaps) produced similar mean steady state plasma digoxin concentrations in ten healthy volunteers. Respective values were 1.07 +/‐ 0.075 and 0.95 +/‐ 0.048 ng ml‐1. 2 During continued administration, peak plasma concentrations occurred earlier after capsules with a tendency to higher peak levels. However, area under curve determinations over 7 h were similar. 3 Approximately 10% less digoxin was recovered in urine collected in a 12 h dosage interval during the lower dosage administration of capsules. Mean percentage urinary recovery of administered dose was 57% for tablets and 65% for capsules. 4 The enhanced bioavailability of Lanoxicaps was associated with reduced between‐subject variability in plasma concentration. 5 Lanoxicaps (0.2 mg) should be approximately equivalent in effect to digoxin tablets (0.25 mg) currently available in the United Kingdom, though improved consistency would be anticipated.
A repeated dose comparison of dichloralphenazone, flunitrazepam and amylobarbitone sodium on some aspects of sleep and early morning behaviour in normal subjects.
Authors: Hindmarch I , Parrott AC , Arenillas L
Published: July 2012

1 Seven normal subjects were given three different hypnotics (flunitrazepam 1 mg, amylobarbitone sodium 100 mg and dichloralphenazone 1300 mg) for four consecutive nights each. 2 All three substances improved subjective assessment of the ease of getting to sleep. Flunitrazepam was rated as better than eithr dichloralphenazone or amylobarbitone sodium in this respect. 3 The perceived quality of induced sleep was not altered by any of the preparations. 4 There was a disturbance of the subjective ratings of getting to sleep following cessation of treatment with dichloralphenazone, giving tentative support to the existence of a ‚rebound’ effect. 5 Dichloralphenazone produced an impairment in psychomotor performance as measured on a complex reaction time test following four nights medication with the drug.
Indirect blood pressure and heart rate measured quickly without observer bias using a semi‐automatic machine (auto‐manometer)‐response to isometric exercise in normal healthy males and its modification by beta‐adrenoceptor blockade.
Authors: Nyberg G
Published: July 2012

1 In a double‐blind crossover study, six volunteers performed sustained handgrip at 50% of maximal voluntary contraction before and 90 min following oral administration of 0.25 and 100 mg metoprolol tartrate, a beta1 selective adrenoceptor blocking agent. Blood pressure and heart rate were measured with the Auto‐Manometer, an electronic semi‐ automatic device based on the principles of the London School of Hygiene and Tropical Medicine sphygmomanometer. It eliminates observer and digital bias completely, and also records heart rate at the same time as blood pressure is recorded. 2 Resting heart rate fell 15% after 25 mg, 21% after 100 mg and was unchanged after placebo. Systolic blood pressure fell 6% on both doses and was unchanged on placebo. Diastolic pressure did not change with any of the doses. 3 At 1 min of handgrip, heart rate was significantly lower after 25 and 100 mg than before drug or after placebo. There was no difference between the blood pressure levels attained before or after any of the dose levels. The rise of heart rate tended to be somewhat dampened after 100 mg only. The rise in blood pressure was unchanged after any dose compared with before.
A comparative trial of clonidine, propranolol and placebo in the treatment of moderate hypertension.
Authors: Wilkinson PR , Raftery EB
Published: July 2012

1 A double‐blind cross over trial between clonidine, propranolol and a placebo in patients with moderate hypertension has been performed. 2 Thirty‐two patients completed the study which consisted of three treatment periods in random order of 3 months each. Patients had their blood pressure recorded by an unbiased observer using a random‐zero machine. 3 Both clonidine and propranolol produced a significant reduction in blood pressure (P less than 0.01), which was apparent by the second week of therapy. Propranolol gave a greater reduction in pulse rate than clonidine (P less than 0.01) but clonidine also reduced the pulse rate significantly (P less than 0.05). There was no evidence of postural hypotension on either drug. Side‐effects were more common with clonidine but these tended to wear off after several weeks of therapy. 4 Clonidine and propranolol were equipotent in reducing blood pressure, but clonidine has more initial side‐effects than propranolol.
Intravenous fluids in medical in‐patients.
Authors: Lawson DH
Published: July 2012

1 Data from the Boston Collaborative Drug Surveillance Program were reviewed to determine the proportion of patients receiving intravenous fluids in the participating hospitals. 2 Wide differences between hospitals in the United States and four other countries were observed: i.v. fluids being given to 54% of patients in one American hospital and only 7% of patients in an Israeli one. A two‐fold difference in the frequency of i.v. fluid use in two otherwise comparable Scottish teaching hospitals was observed. This difference was not due to observed patient characteristics, did not arise from selection bias or observational differences between the two hospitals and was unlikely to have arisen by chance. 3 It is concluded that the findings were due to different policies on the part of the attending physicians. Although the study could not be used to evaluate the beneficial effects of the administered fluids, adverse effects were common (15% of recipients) and in some instances potentially serious. Adverse effects were reported more frequently after infusion of 5% dextrose (13% of recipients) than after isotonic saline (7%) perhaps because of the low pH of the former solution.
A comparison of cholestyramine and nicotinic acid in the treatment of familial type II hyperlipoproteinaemia.
Authors: Mann JI , Harding PA , Turner RC , Wilkinson RH
Published: July 2012

1 The effects of cholestyramine and nicotinic acid on plasma lipid concentration have been compared in patients with type IIa hyperlipoproteinaemia. 2 During a 3‐month period, cholestyramine resulted in a mean decrease in cholesterol levels of 26%. Triglyceride levels rose in eight of the ten patients during treatment with this drug but in the majority of patients remained within the normal range. 3 During nicotinic acid therapy, cholesterol fell by a mean of 21% and triglyceride by a mean of 23%. 4 The slow release preparation of nicotinic acid used was acceptable to the majority of the patients studied and the results therefore suggest that this drug may be a useful alternative to the more widely used agent, cholestyramine.
Determinants of anticoagulant control in patients receiving warfarin.
Authors: O'Malley K , Stevenson IH , Ward CA , Wood AJ , Crooks J
Published: July 2012

1 A hospital‐based drug information system has been used to assess the time for which patients treated with warfarin were outside the range of Thrombotest values 5‐10% and 5‐15% and to examine possible contributory factors in situations where anticoagulation fell outside these ranges. 2 Anticoagulant control varied with the age of the patient and with concomitant drug therapy but not with patient sex or indication of anticoagulation. 3 Most patients were ‘under‐anticoagulated’ at some stage but patients over 70 years spent significantly longer in the 5‐ 10% range than those in the age range 30‐59 years and Thrombotest values of less than 5% were found predominantly in the older group. 4 Patients given drugs known to interact with warfarin spent least time in the defined Thrombotest ranges. Those on drugs known to potentiate warfarin effect had significantly lower Thrombotest values than the other patients studied.
Age as a determinant of sensitivity to warfarin.
Authors: Shepherd AM , Hewick DS , Moreland TA , Stevenson IH
Published: July 2012

1 Parallel human and rat studies were carried out to confirm the previous suggestion of an increased sensitivity to warfarin in old age. 2 The anticoagulant response to warfarin was found to be greater in the elderly groups despite, in the case of the patient study, the elderly subjects being given a smaller weight‐related dose. 3 At the same plasma warfarin concentrations there was greater inhibition of vitamin K‐dependent clotting factor synthesis in the elderly. There was no difference in the rate of clotting factor degradation in the two age groups. 4 There was no appreciable difference in warfarin pharmacokinetics (plasma half‐life, apparent volume of distribution, plasma clearance, plasma protein binding or plasma warfarin alcohol levels) in the two age groups. 5 There appeared to be no major age‐ related differences in warfarin pharmacokinetics and the increased effect of warfarin in the elderly seemed to result from an increased intrinsic sensitivity to warfarin.
Amphetamines, growth hormone and narcolepsy.
Authors: Parkes JD , Debono AG , Jenner P , Walters J
Published: July 2012

1 Plasma amphetamine and growth hormone levels have been measured in eight normal and twenty‐six narcoleptic subjects following a single dose of (+)‐amphetamine (20 mg) or (‐)‐amphetamine (20 mg) by mouth. 2 Peak plasma levels and the shape of the plasma amphetamine‐time curve were similar with both isomers in normal and narcoleptic subjects. 3 In most normal subjects both (+)‐and (‐)‐amphetamine (20 mg) caused an increase in the plasma concentration of growth hormone. The two isomers were approximately equipotent in this respect. Neither (+)‐ nor (‐)‐ amphetamine (20 mg) caused an increase in plasma growth hormone concentration in narcoleptics. 4 Following amphetamine (30 mg), two of six narcoleptic subjects had an increase in plasma growth hormone concentration. 5 Levodopa (250 mg) with (‐)‐alpha‐methyldopa hydrazine 25 mg (Sinemet) by mouth, caused a rise in plasma growth hormone concentration in most normal subjects. The magnitude of the Sinemet‐ induced rise in plasma growth hormone concentration in narcoleptics was less than in normal subjects.
Plasma prednisolone levels in man following administration in plain and enteric‐coated forms.
Authors: Wilson CG , May CS , Paterson JW
Published: July 2012

1 Prednisolone plasma levels were measured in seven patients by a competitive protein binding method after administration of prednisolone (20 mg) by mouth as plain or enteric‐coated tablets. 2 The mean peak plasma prednisolone concentration after the enteric‐coated preparation, 199 ng ml‐1, was significantly lower than after the plain tablet, 268 ng ml‐1, and occurred later, at 4.69 h compared with 1.72 h. The bioavailability of the two preparations was similar. 3 It is concluded that, although the plasma concentration versus time profiles are different, the absorption of prednisolone from plain and enteric‐coated preparations is equal.
The absorption and elimination of ICI 74,917 in man.
Authors: Pickup ME , Johnson AJ , May CS , Paterson JW , Harrison MP
Published: July 2012

1 The pharmacokinetics of ICI 74,917 were studied in both asthmatic patients and normal volunteers. 2 The tritiated compound was administered to the lungs by inhalation from an aerosol and a bronchoscope, and by intravenous, oral and buccal routes. Radioactivity was measured in plasma, urine, faeces, sputum and exhaled air. 3 After bronchoscopic administration 63% of the available dose was absorbed; after aerosol administration 8% was absorbed from the lung and more than 50% swallowed. 5 Intravenous studies indicated that the drug is excreted in the bile and urine in the ratio 2:1. 5 Minimal oral and no buccal absorption occurred. 6 There was no evidence of tritium exchange or drug metabolism. 7 The mean terminal half‐life following administration by all route was 16.1 hours. However, the majority of the dose was rapidly excreted. 8 Aerosol administration is the method of choice for the clinical use of ICI 74,917.
Plasma, bone, hip capsule, synovial and drain fluid concentrations of lincomycin during total hip replacement.
Authors: Parsons RL , Beavis JP , Hossack GA , Paddock GM
Published: July 2012

1 Lincomycin (600 mg) was given 6 h preoperatively by intramuscular injection, as an intravenous infusion over 30 min and for 72 h postoperatively in twelve patients having total hip replacement. 2 The plasma, bone, hip capsule, synovial and drain fluid concentrations of lincomycin were almost always above the M.I.C. of lincomycin against penicillinase producing Staphylococcus aureus. 3 There was a good correlation between the estimated concentrations of lincomycin in bone by the grinding and agitation methods of analysis. 4 Two patients developed pseudomembranous colitis after parenteral lincomycin.
Lignocaine kinetics in cardiac patients and aged subjects.
Authors: Nation RL , Triggs EJ , Selig M
Published: July 2012

1 The pharmacokinetics following long term intravenous infusion of lignocaine to cardiac patients have been examined. 2 Plasma levels and half‐lives of lignocaine and monoethylglycinexylidide (MEGX) showed wide inter‐patient variability. 3 Toxicity reactions to therapy were associated with elevated lignocaine and/or MEGX plasma levels. 4 In a separate study the effect of age on the pharmacokinetics of lignocaine was examined using bolus doses (50 mg) of the drug to young and aged subjects. 5 Elderly subjects had significantly longer half‐lives for lignocaine compared to younger individuals although no change in plasma clearance occurred. 6 The drug appeared to distribute differently in the aged as reflected by significantly increased apparent volumes of distribution. 7 The 24 h urinary recovery of the major metabolite (total 4‐hydroxyxylidine) showed a significant reduction in the elderly when compared to the young. 8 The clinical significance of these studies with respect to lignocaine therapy has been discussed.
Comparison of quinidine plasma concentration curves following oral administration of some short‐ and long‐acting formulations.
Authors: Frigo GM , Perucca E , Teggia‐Droghi M , Gatti G , Mussini A , Salerno J
Published: July 2012

1 The time‐course of quinidine plasma concentrations and selected kinetic parameters were studied in healthy male volunteers given single oral doses of four different quinidine formulations. Comparison was made with quinidine sulphate in a rapidly dissolving form. 2 Plasma half‐lives did not significantly differ among treatments. 3 Quinidine polygalacturonate appears to be equivalent to quinidine sulphate in respect to both the absorption and elimination kinetics. When both quinidine bisulphate (Kinidin Durules) and quinidine arabogalactansulphate (Longacor) were administered plasma levels peaked significantly later than after quinidine sulphate. However, while the former seems to be absorbed to the same extent as quinidine sulphate, the latter exhibits lower bioavailability in respect to all other preparations.
The effect of quadruple chemotherapy on the peripheral blood lymphocyte populations in Hodgkin's disease.
Authors: Clay A , Swain A , Trounce JR
Published: July 2012

1 Quadruple chemotherapy with cytotoxic drugs in advanced (Stage IIIB) Hodgkin's disease causes a fall in the blood lymphocyte count with recovery 1 month after stopping treatment. 2 No selective effect on the T or B lymphocyte populations was shown.
Serum concentrations of lithium after three proprietary preparations of lithium carbonate (Priadel, Phasal and Camcolit).
Authors: Bennie EH , Manzoor AK , Scott AM , Fell GS
Published: July 2012

1 The serum lithium concentration was measured before dosing, and at 2, 4, 6, 8, 10, 20, 22, and 24 h after three proprietary preparations of lithium carbonate (Camcolit, Phasal or Priadel). 2 A total of twenty‐ eight studies were performed on eleven patients. In seven studies the patients received Camcolit, in ten studies patients received Priadel and in eleven the patients took Phasal. 3 The dose of each preparation was adjusted during a 10 week run‐in period to maintain the serum lithium within the normal therapeutic range (0.6‐1.2 mmol/1). Five patients received one lithium preparation, one patient received three lithium preparations and five patients received four lithium preparations consecutively. 4 After a single daily dose of Phasal and Priadel, the serum lithium remained within the therapeutic range for 24 h. 5 After a single daily dose of Camcolit, the serum lithium remained within the therapeutic range for only 12 h. 6 After three doses of Camcolit (given at 0.800 h, 12.00 h, and 18.00 h) each day, the serum lithium was maintained in the therapeutic range for 24 h.
Acebutolol metabolite plasma concentration during chronic oral therapy.
Authors: Winkle RA , Meffin PJ , Ricks WB , Harrison DC
Published: July 2012

1 We have measured the plasma concentration of acebutolol and a major metabolite in patients on chronic oral therapy with this drug, using a new assay, specific for each species. Our study suggests: 2 The acetyl metabolite was present in concentrations greater than those of acebutolol at all times during the dosing interval in all seven subjects. 3 The ratio of the mean steady‐state plasma concentrations of the acetyl metabolite to unchanged acebutolol was 2.7 +/‐ 1.0. 4 Previous studies using non‐specific methods that measure plasma concentrations of the acetyl metabolite and acebutolol as a single species cannot be used to determine pharmacokinetic parameters or to provide reliable correlations of plasma drug concentration with effect. 5 Future studies determining plasma concentration of acebutolol should take this metabolite into account. 6 Further work will be necessary to determine the metabolite's contribution to acebutolol's effects in man.
Atenolol once‐daily in hypertension.
Authors: Jeffers TA , Webster J , Petrie JC , Barker NP
Published: July 2012

1 The effect of atenolol, a cardioselective beta adrenoceptor antagonist, was studied in a double‐blind crossover trial in twenty‐one carefully selected hypertensive outpatients. Each patient received atenolol (50 mg/day, 100 mg/day, 200 mg/day) and placebo according to a randomized sequence in a once‐daily dose. Wash‐out periods on a matching placebo were included between the treatment periods. 2 The effect of lying, standing and post‐exercise blood pressure of atenolol 50 mg once‐daily was not significantly different from atenolol 100 or 200 mg once‐daily. The reduction in lying and standing blood pressure was approximately 23/16 and 22/18 mm Hg from levels at the end of a run‐ in period on matching placebo of 167/108 and 162/112 mm Hg respectively. 3 The study shows that atenolol is an effective hypotensive agent in a once‐daily dose.
Metabolic effects of fenfluramine in obese diabetics.
Authors: Larsen S , Vejtorp L , Hornnes P , Bechgaard H , Sestoft L , Lyngsoe J
Published: July 2012

1 In a single‐blind, cross‐over study fenfluramine in a daily dose of 120 mg was found to reduce the daily blood glucose level moderately in hospitalized obese diabetics treated with a 1200 calorie diabetic diet. 2 After 7 days of treatment, fenfluramine was found not to influence the intravenous glucose tolerance, the insulin response to intravenously administered glucose, or the growth hormone response to arginine. 3 No changes in blood levels of lactate, beta hydroxybutyrate, triglycerides or cholesterol were seen during fenfluramine treatment.
Factors influencing plasma phenobarbitone levels in epileptic patients.
Authors: Eadie MJ , Lander CM , Hooper WD , Tyrer JH
Published: July 2012

1 Various statistical techniques were used to study the effects of age, sex and concurrent therapy with other anticonvulsants on the relation between plasma phenobarbitone levels and doses of (i) phenobarbtione, (ii) methylphenobarbitone or (iii) primidone, in epileptic patients. 2 Methylphenobarbitone and primidone are converted to phenobarbitone in the body. The mean doses of phenobarbitone, methylphenobarbitone and primidone which produced the same plasma phenobarbitone level (15 microgram/ml) were, respectively, 1.75,2.75 and 7.75 mg kg‐1 day‐1. 3 For both phenobarbitone and methylphenobarbitone dose requirement to achieve a given plasma phenobarbitone level fell progressively with age. Sex influenced the relation between plasma phenobarbitone level and phenobarbitone or methylphenobarbitone dose. Interactions were detected between primidone and both phenytoin and carbamazepine. 4 In individual patients, within the limits of dosage studied, the relation between plasma phenobarbitone level and drug dose was not rectilinear if phenobarbitone itself was taken, but was rectilinear if methylphenobarbitone was taken.
A spectrofluorometric method for the determination of ajmaline in plasma.
Authors: Welman E , Curry PV , Krikler DM , Rowlands E , Callowhill EA
Published: July 2012

1 Ajmaline was found to have maximum fluorescence at neutral pH with 300 nm excitation and 365 nm emission wavelengths (corrected). 2 The fluorescence intensity had a linear relationship to concentration up to 50 microgram ml‐1 and the recovery of ajmaline after extraction from plasma was 92.5 +/‐ 3%. 3 Extraction of drug‐free plasma and of samples containing known concentrations of ajmaline showed that drug levels in the range found clinically could be measured accurately by fluorimetry. 4 Serial plasma ajmaline concentrations were measured in a subject after intravenous injection of ajmaline (50 mg). The rates of plasma clearance of the drug were found to be similar to those obtained in previous studies.
Effect of the 1,5‐benzodiazepines, clobazam and triflubazam, on sleep in man.
Authors: Nicholson AN , Stone BM , Clarke CH
Published: July 2012

1 The effect of the 1,5‐benzodiazepines, clobazam (10 and 20 mg) and triflubazam (20 and 40 mg), on sleep was studied in six healthy males using electroencephalography for sleep measures and analogue scales for subjective assessments of well being and sleep quality. The effect of clobazam was limited to the night of ingestion. There was some evidence from subjective assessments that the effect of triflubazam may have persisted beyond the night of ingestion. 2 No effect of clobazam or triflubazam was observed on total sleep time, stage shifts in the first 6 h or latency to the first rapid eye movement period of sleep. With clobazam sleep onset latency was shortened (P less than 0.05), but this effect was not seen with triflubazam. The latency to stage 3 was shortened by both drugs. There was evidence of reduced duration of awake (stage 0) activity and drowsy (stage 1) sleep with both drugs. 3 The percentage stage 1 sleep was reduced by clobazam (10 and 20 mg) and by triflubazam (20 mg) (P less than 0.05), though the effect was not significant with triflubazam (40 mg). Clobazam (20 mg) increased the percentage stage 2 sleep (P less than 0.05), but reduced the percentage stage 3 (P less than 0.01) and stages 3 + 4 (P less than 0.05) sleep. There were no other effects on percentage of total sleep time occupied by various sleep stages or in duration (min) of sleep stages, except that the duration (min) of sleep stages, except that the duration (min) of stage 2 sleep in the second 2 h interval of sleep was increased with clobazam (20 mg) (P less than 0.01). 4 Subjects reported impaired sleep with triflubazam (40 mg) (P less than 0.05), and a sense of less wakefulness the morning after ingestion of clobazam (10 and 20 mg) (P less than 0.01) and triflubazam (40 mg) (P less than 0.05).
Preliminary studies of absorption and excretion of benoxaprofen in man.
Authors: Smith GL , Goulbourn RA , Burt RA , Chatfield DH
Published: July 2012

1 Benoxaprofen is a new acidic anti‐inflammatory compound which was well absorbed after oral administration to man. 2 Single doses of 100, 200 and 400 mg produced mean peak concentrations in the plasma of 13.0, 33.5 and 45.3 microgram respectively, and the plasma half‐life of the compound was between 30 and 35 hours. 3 Multiple dosing with 25 and 50 mg every 24 h achieved an equilibrium conentration in the plasma after 6‐8 days, while dosing with 100 mg every 12 h enabled equilibrium to be reached in 3‐6 days. Plasma concentrations between 35 and 45 microgram/ml were achieved by giving 100 mg doses every 12 hours. 4 Absorption of benoxaprofen was delayed when the drug was given with food, but the total amount absorbed remained the same. 5 The effect of milling the material to small particle size (19 micron) was to increase the rate of absorption compared to that of unmilled material (58 micron). 6 Benoxaprofen was well tolerated by healthy male subject in the doses given.
Hydroxyethyl starch. An agent for hypovolaemic schock treatment II. Urinary excretion in normal volunteers following three consecutive daily infusions.
Authors: Mishler JM , Borberg H , Emerson PM , Gross R
Published: July 2012

1 Urinary hydroxyethyl starch (HES) concentrations were determined by the anthrone method, in four healthy normal male volunteers following three consecutive daily 500 ml infusions (total 1500 ml), in order to ascertain excretion rates under normal controlled conditions. 2 The HES was excreted at a rate of 2.57, 2.46, and 2.44 g/h during the first hour postinjection, on days 1, 2, and 3, respectively. 3 The rate during the interval 12‐24 h postinjection, averaged 0.14, 0.21, and 0.10 g/h, on days 1,2, and 3, respectively. 4 In the intervals 24‐72, 72‐120, and 120‐168 h after the third and final injection, the excretion rate was 0.07, 0.04, and 0.02 g/h, respectively. 5 Renal function, as assessed by serum creatinine and uric acid concentrations and 24 h void volumes, was normal during the entire period of observation. 6 The results indicate that HES is excreted at a similar rate following three consecutive daily infusions without evidence of renal injury.
Further studies of rimiterol and salbutamol administered by intermittent positive‐pressure ventilation, and an important observation on the technique of using the Bennett ventilator.
Authors: Paterson IC , Willey RF , Shotter MV , Crompton GK
Published: July 2012

1. Using the same technique of administering drugs by intermittent positive‐pressure ventilation as used in previous studies a source of contamination of solutions nebulized was discovered. This was rectified by using a new ventilator and completely separate patient circuits for each solution nebulized. 2 Salbutamol 0.5% and 0.25% solutions achieved the same degree of bronchodilatation, but there was a significantly greater increase in heart rate produced by salbutamol 0.5%. 3 Rimiterol 0.5% and salbutamol 0.25% produced similar peak mean improvements in FEV and also induced the same degree of tachycardia, but the duration of these effects were significantly shorter in the case of rimiterol. 4 The sustained degree of bronchodilatation achieved by salbutamol 0.25% could not be mirrored by giving two doses of rimiterol 0.5%, the second dose 2 h after the first. 5 Rimiterol 0.5% induced a degree of tachycardia which was similar in peak effect to that observed after salbutamol 0.25%. However, in the controls the second dose of rimiterol, given 2 h after the first, was responsible for only a small increase in heart rate which was not significantly different than that after saline in the other three treatment groups.
The disposition of sodium fusidate in man.
Authors: Wise R , Pippard M , Mitchard M
Published: July 2012

1 In a pharmacokinetic study in six volunteers serum fusidic acid concentrations were obtained after rapid intravenous administration of 100 mg. 2 Analysis of the data suggests that the serum concentration/time curve is biphasic and that the curve can be described by the following equation: cp=5.9e(‐1.82t)+4.3e(‐0.13t). 3 The disposition characteristics of sodium fusidate have been calculated from this relationship and a plasma half life for sodium fusidate of between 5 and 6 h obtained. 4 Subsequently plasma fusidic acid levels have been measured in the same volunteers on three occasions after sodium fusidate (500 mg) given either as a slow intravenous infusion, or orally as a capsule or as a suspension. 5 Serum levels and AUC after a capsule were about 75% of those obtained after the infusion (30 and 70 mg/1 at peak respectively) whereas levels and AUC after the suspension were only about 50%.
The clinical pharmacology of mexiletine.
Authors: Campbell NP , Kelly JG , Adgey AA , Shanks RG
Published: July 2012

1. Mexiletine was given to 156 patients by intravenous or oral routes of administration. 2. There was great interpatient variation in kinetics and plasma concentrations with both routes of administration. 3. The mean volume of distribution was 6.63 l/kg. The mean plasma elimination haf‐life after chronic oral therapy was 11.31 h. 4. Plasma concentrations between 0.75 and 2.00 microgram/ml were usually effective. Within this therapeutic range severe side effects were uncommon. 5. Plasma concentrations within this range were achieved in 72% of patients when doses of 10–14 mg‐1 kg‐1 day were given orally.