bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personality traits and theophylline metabolism
Authors: Hartzema Abraham G. , Pancorbo Sal , Davis Scott 
Published: October 2006

AbstractThe objectives of this study were to investigate the relationship between personality trait variables and theophylline disposition in asthmatic patients.Twenty‐five patients admitted to a hospital who required intravenous theophylline for bronchodilation were studied. Data on theophylline half‐life, and the patients' histories on congestive heart failure, liver disease, and smoking behaviour were abstracted. Eysenck's personality inventory was administered to obtain a score on the two personality traits: neuroticism and extroversy.High neurotic patients showed a significantly (p< 0.005) lower theophylline half‐life. Neuroticism appeared to be, in this patient population, a more important determinant of theophylline half‐life than variables such as congestive heart failure, liver disease, or smoking behaviour.
Bioavailability of bemetizide and triamterene from a combination formulation
Authors: Brodie R. R. , Chasseaud L. F. , Darragh A. , Taylor T. , Walmsley L. M. 
Published: October 2006

AbstractThe bioavailability of the thiazide diuretic bemetizide from a tablet containing 25 mg of this drug and 50 mg of the chemically unrelated diuretic triamterene was lower than, and significantly different (P < 0.01) from that from a tablet containing 25mg bemetizide alone. The mean peak plasma level of bemetizide after administration of the combination tablet (68.3ngml−1) was lower than that after administration of bemetizide alone (87.9 ngml−1), although the times of occurrence of the peak levels were similar. The bioavailability of triamterene from the combination tablet was greater than, but not significantly different from that after administration of a capsule containing 50 mg triamterene alone. The mean peak plasma level of triamterene after administration of the combination tablet (44.6 ng ml−1) was higher than and significantly different (p< 0.001) from that after administration of triamterene alone (15.7 ng ml−1). Although bemetizide is unstable in urine, measurement of the apparent excretion of unchanged drug in the 24 h post‐dose urine (less than 4 per cent of the dose) agreed with the estimate of drug bioavailability from the plasma level data. Less than 2 per cent of the dose of triamterene was excreted unchanged in the 24 h post‐dose urine, but the urinary excretion data also agreed with the bioavailability estimates from the plasma level data.The results of this study and those reported in the literature suggest that because of their physicochemical properties, the bioavailability of some thiazides and triamterene needs to be evaluated when new formulations of these drugs are produced. However, with respect to the combination formulation reported in this paper, the difference in bioavailability of the thiazide component did not detectably effect the diuretic activity of the formulation.
The pharmacokinetics of chlorbutol in man
Authors: Tung C. , Graham G. G. , Wade D. N. , Williams K. M. 
Published: October 2006

AbstractThe pharmacokinetics of chlorbutol were studied after oral administration in 4 healthy subjects on two occasions. Following the rapid attainment of peak concentrations, plasma concentrations fell by approximately 50 per cent in 24 h. After the first dose of chlorbutol, the terminal elimination half‐life was 10.3 ± 1.3 days (mean ± S.E.M), the volume of distribution was 233 ± 141 and the plasma clearance was 11.6 ± l.0 ml min −1. The binding to plasma proteins was 57 ± 3 per cent. In 3 of the 4 subjects, there was a small but significant decrease in the terminal half‐life of chlorbutol after the second dose. The mean urinary recovery over 17 days in two of the subjects accounted for only 9.6 per cent of the dose, 7.4 per cent of the total as the glucuronide and sulphate conjugates and 2.2 per cent as unchanged chlorbutol. A significant factor in the elimination of chlorbutol may be its instability under physiological conditions. Its half‐life in vitro is 37 days at pH7.4. The long terminal half‐life of chlorbutol makes it unsuitable as a sedative drug because of the considerable accumulation which will occur when the drug is taken in multiple doses.
Some novel observations of a drug (indoprofen)—albumin interaction
Authors: Juni K. , Nieves E. A. , Perrin J. H. 
Published: October 2006

AbstractIndoprofen, a new‐steroidal anti‐inflammatory agent, binds to human serum albumin in an endothermic reaction at low degrees of saturation and with an exothermic reaction at higher drug to protein ratios. Although indoprofen appears to bind to the same primary site as diazepam, dialysis studies show an increased binding of both drugs in the presence of the other. This novel observation is probably due to the effect of the drugs on the N → B conformational change of human serum albumin.
Pharmacokinetics of two lorazepam formulations, oral and sublingual, after multiple doses
Authors: Caillé G. , Spénard J. , Lacasse Y. , Brennan J. 
Published: October 2006

AbstractThe pharmacokinetic profiles of a sublingual and a conventional oral lorazepam tablet formulation were established following chronic administration to twelve healthy male volunteers. Fitting a multi‐dose equation based on a one‐compartment model to the observed data, the average elimination half‐lives for the sublingual and oral doses are estimated to be 11 and 8 h, respectively, while the corresponding absorption half‐lives are 15 and 55min; this confirms earlier reports that the sublingual formulation is more rapidly absorbed.The observed time to steady‐state for both formulations was approximately 3 days, which agrees well with that predicted from previous single dosing studies. Although the sublingual formulation yields a higher average steady‐state minimum plasma concentration than the oral formulation (41·6 versus 38·1 ngml−1), the maximum lorazepam concentration achieved during steady state was approximately 83 ng ml−1 for both formulations. The average steady‐state plasma concentration is estimated to be 63ngml−1, independent of the formulation used.
Human platelet response to three salicylate dosage forms
Authors: Thiessen J. J. , Grad H. , Macleod S. M. , Spino M. 
Published: October 2006

AbstractAcetylsalicylic acid (ASA) inhibition of platelet aggregation as evaluated by collagen‐induced 14C‐serotonin release, has been measured in 12 healthy male subjects. Each subject received a single oral dose (650 mg) of enteric‐coated ASA (ecASA) and compressed ASA tablets (cASA), or ecASA and sodium salicylate (578 mg) separated by a minimum of 5 weeks. The platelet response was related to plasma ASA and salicyclic acid determined by high‐pressure liquid chromatography. Both ecASA and cASA inhibited 14C‐serotonin release; no significant difference was observed in the maximum effect between these two products (p > 0·05). No relationship was found between the maximum observed plasma ASA level and the maximum effect. Further, no correlation was found between the maximum inhibition of 14C‐serotonin release in vivo and the release predicted from in vitro experiments wherein the effect was measured after incubating plasma containing specified ASA concentrations.
Studies on aminophylline disposition I. A rapid and sensitive HPLC assay for ethylenediamine in plasma and urine
Authors: Cotgreave Ian A. , Caldwell John 
Published: October 2006

AbstractA simple and rapid assay for ethylenediamine in plasma and urine is described. Ethylenediamine is treated with m‐toluoyl chloride, yielding its N,N′‐di(m‐toluoyl) derivative, which is extracted into dichloromethane and assayed by reversed‐phase high pressure liquid chromatography (HPLC) with u.v. detection. Quantitation is achieved with reference to the corresponding derivative of cadaverine as internal standard. The assay is reproducible, and the lower limit of detection is 0·05 μg ml−1 Calibration curves in plasma and urine are linear over the concentration range 0·05–100 μg ml−1 The assay has been applied to the analysis of ethylenediamine in plasma and urine following the administration of aminophylline orally and intravenously to a volunteer.
Influence of concentration‐dependent protein binding on serum concentrations and urinary excretion of disopyramide and its metabolite following oral administration
Authors: Haughey David B. , Lima John J. 
Published: October 2006

AbstractConcentrations of disopyramide (D) and mono‐N‐dealkyldisopyramide (MND) were measured in serum and urine following administration of 100, 150, 200, and 300 mg D to four volunteers. The free fraction of D in serum was drug concentration‐dependent in all four subjects following the administration of the four doses. Areas under the free (unbound) D serum concentration‐time curves (AUC) were linearly related to dose following 100–200 mg D. AUC values were 30–60 per cent higher than expected in two subjects following 300 mg D due to an apparent dose‐dependent decrease in D renal tubular secretion. Renal clearance of free D averaged 10·91h−1. The renal clearance of MND averaged 10·31h−1. The urinary excretion of MND was proportional to disopyramide dose.
Intestinal lymphatic absorption of cyclosporin a following oral administration in an olive oil solution in rats
Authors: Ueda Clarence T. , Lemaire Michel , Gsell Guy , Nussbaumer Kurt 
Published: October 2006

AbstractThe intestinal lymphatic absorption of cyclosporin A (CyA) following oral adminstration of 6·5 0·6 and 25·2±1·4mg kg−1 doses of the drug dissolved in an olive oil solution was studied using a thoracic duct‐cannulated rat model. Cumulative lymph samples were collected for up to 114h post‐dosing and assayed by liquid scintillation counting. In this study, the estimated amount of lymphatically absorbed CyA was 0·35±0·13 and 0·47±0·29 per cent of the respective doses. In terms of the overall oral bioavailability of CyA (Fpo) by all absorptive mechanisms, the intestinal lymphatics accounted for the absorption of approximately 2 per cent of the total amount of absorbed drug. Fpo was 21·3±2·5 per cent. The results of this study suggested that lipophilicity alone was not the only factor governing intestinal lymphatic drug absorption. An explanation for the low level of lymphatic CyA absorption is presented. In addition, some reasons for the low overall oral bioavailability of CyA are discussed.
Interaction of norethindrone and isoniazid following their oral co‐administration to the minipig
Authors: Loo J. C. K. , Jordan N. , Menzies J. A. , Watanabe H. 
Published: October 2006

AbstractFollowing the oral co‐administration of isonicotinic acid hydrazide and norethindrone to minipigs, the hydrazone of norethindrone was detected in plasma as its p‐methoxybenzaldehyde derivative, using a high performance liquid chromatographic technique. The suspected precursor of the hydrazone of norethindrone was isonicotinyl hydrazone of norethindrone, a reaction product probably formed between norethindrone and isonicotinic acid hydrazide in the acid environment of the stomach. An in vitro liver metabolite of isonicotinyl hydrazone of norethindrone was isolated following derivatization with p‐methoxybenzaldehyde and characterized by high resolution mass spectrometric and radiochemical techniques. The results demonstrated that the hydrazone of norethindrone is a metabolite of isonicotinyl hydrazone of norethindrone.
Valproic acid pharmacokinetics in the mouse following controlled‐release of pharmacologic and toxic doses via novel implantable and refillable drug reservoirs
Authors: Nau Heinz , Finley Paul , Williams Jane , Brendel Klaus 
Published: October 2006

AbstractNovel drug reservoirs are described which, after their implantation under mouse skin, continuously released organic liquids such as the anti‐epileptic drug valproic acid at preselected rates for periods up to several weeks. The liquids, which were filled into the reservoirs, diffused through silastic membranes. The area and thickness of these membranes determined the administered dose. Administration of the anti‐epileptic drug valproic acid at various selected doses resulted in persistent drug concentrations spanning from subtherapeutic to toxic levels. The drug reservoirs were easily refillable in situ which greatly extended the duration of the experiment. The dose administered could be determined within 5–15 per cent (rel. S.D.). It is suggested that the maintenance of persistent drug levels in small laboratory animals may be an appropriate model for the pharmacological and toxicological study of those compounds with short half‐lives and high clearance rates in these species.
Pharmacokinetics of urea: Development of a kinetic model for correlating dietary nitrogen intake and urea metabolism in chronic renal failure
Authors: Lee Ching‐San C. 
Published: October 2006

AbstractA simple urea pharmacokinetic model is developed to define the multiple correlations among dietary nitrogen intake, urea generation rate, and serum urea nitrogen. Model‐based patient data are simulated during and between dialysis for serum urea nitrogen. Application of the kinetic model is demonstrated by retrospective fitting of serum urea nitrogen to the simultaneous equations which pertain to the model. The pharmacokinetic parameters obtained through the computer fitting can be integrated according to the mass balance equation to yield a quantitative solution to achieving the regulation of protein nitrogen intake. The kinetic approach is potentially advantageous over the conventional nitrogen balance method by virtue of its simplicity. Further validation of the pharmacokinetic model is required before its clinical application.
Pharmacokinetics of mepindolol administered alone and in combination with hydrochlorothiazide—a bioequivalence study
Authors: Krause W. , Lennert Chr. 
Published: October 2006

AbstractThe bioavailability and pharmacokinetics of 10 mg of mepindolol sulphate and of 25 mg of hydrochlorothiazide were compared in a cross‐over design in five healthy volunteers after the administration of either the single drugs (Corindolan® and Esidrix®) or in combination (Tenesor®).Maximum concentrations of mepindolol in the plasma of 25 ng ml−1 were achieved 1·6 h after both treatments and the half‐life of disposition was calculated to be 4·5 h, being somewhat longer after the combination tablet. The amount of hydrochlorothiazide renally eliminated up to 48 h after drug intake was about 60 per cent of the dose. The half‐life of renal excretion was 3 h. The two formulations of mepindolol sulphate and hydrochlorothiazide proved to be bioequivalent with a tendency to better mepindolol bioavailability in the combination form.
Plasma levels of ethaverine after oral administration to humans
Authors: Meyer Marvin C. , Raghow Gursharan , Straughn Arthur B. 
Published: October 2006

AbstractFourteen healthy human subjects received a 200 mg oral dose of ethaverine hydrochloride as an elixir. Blood samples were obtained for 12 h after dosing. Plasma ethaverine concentrations were determined using a paired‐ion, reversed‐phase high performance liquid chromatographic method. Individual plasma concentration‐time profiles were fitted to a two‐compartment model with first‐order absorption. The ethaverine was rapidly absorbed, based on a time of maximum plasma concentration of 0·75 h, a time‐lag of 8·4min, and an apparent first‐order absorption half‐life of 8·6min. The mean terminal elimination half‐life was 3·3 h.
A second peak in uptake of gentamicin by rat kidney after cessation of treatment
Authors: Chareul C. , Faccini J. , Monro A. , Nachbaur J. 
Published: October 2006

AbstractGentamicin was administered s.c. to rats once daily for 7 days at 5 mg kg−1. At the end of this period renal concentrations of gentamicin declined from day 1 to day 5 post‐dosing, but showed a second peak on day 8, after which they declined again through days 16 and 22. This second peak coincided with a peak of mitotic activity in the kidney, suggesting that this organ, while recovering from gentamicin‐induced damage, passes through a temporary phase during which it has increased affinity for gentamicin.
A bioequivalency study of two trifluoperazine tablet formulations using ria and GC–MS
Authors: Midha K. K. , Hawes E. M. , Korchinski E. D. , Hubbard J. W. , McKay G. , Cooper J. K. , Roscoe R. M. H. 
Published: October 2006

AbstractTwo sensitive analytical procedures, a radioimmunoassay (RIA) and a mass fragmentographic (GC–MS) method, were used to quantitate plasma trifluoperazine concentrations over 24 h in five healthy male volunteers following single 5 mg doses of two trifluoperazine tablet formulations (A and B) in a two‐way cross‐over design. Bioavailability in terms of area under the plasma concentration versus time curve to 24 h or extrapolated to infinity, maximum plasma concentration and time to maximum plasma concentration using either RIA or GC–MS was not statistically significantly different from one formulation to the other. Also, there were no statistically significant differences between GC–MS and RIA values for AUC024 and Cmax for each of the two formulations examined. However, the mean AUC024 RIA/GC–MS ratios for formulations A and B were 3·1 and 3·4, respectively, while the mean Cmax RIA/GC–MS ratios were 1·7 and 2·1, respectively. These differences in AUC and Cmax are probably mainly due to the relative non‐specificity of the RIA antiserum. Thus, where GC–MS is preferred for pharmacokinetic studies, both analytical procedures can be used for comparative single‐dose bioequivalence studies of trifluoperazine. However, both the methods should be tested in patients in order to establish the suitability of one procedure over the other for the study of plasma level versus clinical response correlations.
Interaction of naproxen with cholestyramine
Authors: Calvo M. V. , Dominguez‐Gil A. 
Published: October 2006

Abstract‘In vitro’ and ‘in vivo’ studies were used to determine the interaction of naproxen, an anti‐inflammatory agent, and cholestyramine, a hypocholesterolemic substance.Cholestyramine shows a marked affinity for naproxen and the intensity of this is governed by the pH values. The maximum amount of naproxen adsorbed by the resin is close to 2·2 mMg−1.The pharmacokinetics of naproxen was studied in eight healthy volunteers after concurrent oral administration in a single dose of 250 mg of naproxen and 4 g of cholestyramine. The resin causes an important delay in the incorporation of naproxen into the systemic circulation, though no significant modifications are seen to take place in any other pharmacokinetic parameters of the drug.
Bioavailability of nifedipine: A comparison between two preparations
Authors: Zylber‐Katz E. , Koren G. , Granit L. , Levy M. 
Published: October 2006

AbstractIn a random cross‐over study, eight healthy volunteers received single 10 mg doses of either nifedipine capsule (Adalat, Bayer) or nifedipine tablets (Taro) after an overnight fast. The areas under the serum concentration time curves were not significantly different (AUC0→ ∞ 319·8 ± 28·0 (SEM) ng ml−1 h−1 for capsules, 260·8 ± 15·3 ng ml−1 h−1 for tablets). The peak serum levels and the time of their occurrence were 162·4 ± 23·4 ng ml−1 at 30 min for capsules and 43·0 ± 3·0 ng ml−1 at 1–2 h for tablets, indicating that the absorption of nifedipine from the capsule is faster than from the tablet form. Clinical symptoms of vasodilation corresponded with the nifedipine peak levels. We conclude that although the bioavailability in general of the two preparations is similar, the therapeutic equivalence may differ. Depending on the therapeutic indication each preparation may have its merits.
Comparative bioavailability of two oral formulations of flurazepam in human subjects
Authors: Cooper Sam F. , Drolet Daniel , Dugal Robert 
Published: October 2006

AbstractThe systemic availability of an investigational oral formulation of flurazepam was compared to that of a commercially available product whose therapeutic efficacy has been well established by usage. The experiment was designed to dissociate formula on factors from all other sources of variation including differences between subjects, sexes, sequences of administration, experimental periods, as well as sex by sequence, sex by period, and sex by formulation interactions. Systemic availability was assessed by conventional pharmacokinetic techniques.Pharmacokinetic interpretation and statistical analysis of plasma concentrations of flurazepam and its major blood metabolites namely N‐1‐hydroxyethylfurazepam and N‐1‐desalkylflurazepam as a function of time and of systemic availability indicators revealed a nearly identical biopharmaceutical behaviour for the two preparations. A significant difference could be seen in the plasma levels of N‐1‐desalkylfurazepam between male and female subjects. The results collectively indicate a very similar biopharmaceutical performance of the two oral formulations of flurazepam.
Effect of quinidine on the intestinal secretion of digoxin in guinea pigs
Authors: Schäfer S. G. , Fichtl B. , Doering W. 
Published: October 2006

AbstractFollowing i.v. injection of digoxin (10 μg kg−1) the ratio between digoxin concentrations in the lumen of jejunal loops perfused in situ and in plasma (L/P) of guinea pigs increased linearily with time. After 3 h, L/P was 8·7, indicating net secretion of digoxin against a concentration gradient. In quinidine treated animals (100 mg kg−1 p.o., 2h before experiment) both the L/P ratio (5·7; p < 0·01) and the digoxin content of jejunal tissue (– 32 per cent; p < 0·01) were markedly reduced. It is suggested that quinidine reduces the extrarenal clearance of digoxin at least in part by inhibiting the intestinal secretion of this glycoside.
Pharmacokinetics of valpromide in dogs after various modes of administration
Authors: Bialer Meir , Rubinstein Abraham 
Published: October 2006

AbstractValpromide‐Depropylacetamide was administered to five dogs via five modes: Three oral formulations (solution, capsule, and enteric‐coated tablet), intravenous and intra‐muscular injections. No significant change in the terminal half‐life of valpromide could be observed after the various modes of administration in each dog. Valpromide was more rapidly absorbed after the administration of an oral solution than after i.m. injection. Similar data also were obtained for its metabolite—valproic acid. It was shown that valpromide in the dogs was partly biotransformed to valproic acid. The average fraction of valpromide that was transformed to valproic acid (fm) ranged from 30–35 per cent after all the oral and parenteral administrations, except for the enteric‐coated tablet, which showed a very low bioavailability of valpromide.
Effects of penicillins on binding of phenytoin to plasma proteins in vitro and in vivo
Authors: Arimori K. , Nakano M. , Otagiri M. , Uekama K. 
Published: October 2006

AbstractEffects of penicillins on the binding of phenytoin to plasma proteins were examined in vitro and in vivo. The results from in vitro studies showed that the penicillins including oxacillin and dicloxacillin were effective in displacing phenytoin from its binding sites. In vivo, the total phenytoin concentration in serum decreased during penicillin administration, while the free phenytoin concentration increased. As a result, penicillins caused a significant increase in the apparent volume of distribution and in the total body clearance of phenytoin. These results can be explained on the basis of the displacement of phenytoin from its plasma protein binding site by penicillins.