摘要:

AbstractA review of the use of cisplatin in cancer chemotherapy in humans is presented. The emphasis is placed on the chemistry,in vivodistribution and biotransformation of this agent. The existing literature pertinent to the physicochemical properties of cisplatin and structure activity relationships of platinum coordination complexes is reviewed. The chemistry of this drug, both in aqueous media and in biological systems is discussed as well as current analytical methodology used for monitoring ‘cisplatin levels’ in biological fluids. Recent advances in analytical methodology specific for cisplatin are also presented and recent findings in the area of the possible biotransformations of this important anticancer agent are discus

ISSN:0142-2782    

DOI:10.1002/bdd.2510020102

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractA gas‐chromatographic (g.l.c.) method with electron‐capture (e.c.) detection is described for the simultaneous quantitative determination of nanogram concentrations of 2‐ethylamino‐3‐phenyl‐norbornane (Fencamfamine, REACTIVAN®) and its metabolite 2‐amino‐3‐phenylnorbornane in urine.The renal excretion of fencamfamine and its metabolite after oral administration to humans was followed over a period of several days. The excretion of both substances was affected by urinary pH. Excretion peaks were obtained 2–4 h after ingestion and the total amount excreted during 80 h varied from 11.9 to 33.2 per cent. Based on urinary values, the biological half life of fencamfamine was 16 h.The intake of acetazolamide shortly after fencamfamine resulted in a decrease of the fencamfamine excretion and a suppression of the metabolite output during at least 10 h. Acetazolamide did not influence the percentage of the doses excreted during 80 h.No changes occurred in urinary fencamfamine or metabolite concentrations during storage of the urine

ISSN:0142-2782    

DOI:10.1002/bdd.2510020103

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractThe metabolism and pharmacokinetics of intravenously administered theophylline (100 mg) have been investigated in three healthy male volunteers who consumed 6 bottles day of a cola beverage, in addition to their usual intake of methylxanthines, for 7 days prior to and during the study. Five urinary metabolites were detected in addition to unchanged theophylline, that is 3‐methylxanthine, 1.3‐dimethyluric acid, 1‐methyluric acid, and two minor unknown metabolites. The elimination of theophylline, 1.3‐dimethyluric acid, 1‐methyluric acid, and the two unknowns was described by first‐order kinetics, whereas that of 3‐methylxanthine was described by Michaelis‐Menten kinetics. The results have been compared with those previously obtained in the same volunteers while consuming their usual intake of methylxanthine‐containing foods and beverages, and this shows that the addition of extra methylxanthines to the diet does not influence the disposition of theophylline. This is in marked contrast to the effect of deprivation of dietary methylxanthines on theophylline metabolism. The results are discussed in terms of the influence of methylxanthines on theophylline metabolism, and of its possible

ISSN:0142-2782    

DOI:10.1002/bdd.2510020104

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractIn this comparative bioavailability study two sustained release capsule formulations of propranolol, one a clinical trial formulation and the other the U.K. sales formulation (‘Inderal’ LA), were compared with a conventional ‘Inderal’ tablet. Twelve healthy adult male volunteers received, on a cross‐over basis, on three separate occasions, 160 mg oral doses of three formulations of ‘Inderal’. Bioavailability was based on concentration of propranolol in whole blood. The peak blood level and area under the propranolol blood level curve fell as the dissolution time increased. The half‐lives of the three formulations were inversely proportional to their dissolution rates, those of the sustained release formulations being considerably longer than that of the conventional tablet.The 160 mg ‘Inderal’ tablet produced a rapid 90‐fold decline over 24 h in propranolol blood levels following a high initial peak. By comparison both sustained release formulations showed a less rapid fall in systemic levels and gave higher blood levels at the end of 24 h and plateau values between 8 and 14 ng ml−1.The ‘Inderal’ LA sustained release formulation gave consistently higher propranolol blood levels than the clinical trial sustained release formulation. This result is in good agreement with their dissolution profiles. The lowering of the systemic bioavailability as the dissolution time increases is thought to be due to an increase

ISSN:0142-2782    

DOI:10.1002/bdd.2510020105

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractA radioimmunoassay has been developed for propranolol with a sensitivity of 2.37nmol l−1in unextracted plasma using a 50 μl sample. Plasma concentration measurements were made on samples from volunteers for up to 8 h after they had been given 5, 10, or 40 mg of propranolol by mouth. Analysis of the results showed that mean elimination half‐lives and total body clearances were similar following each of the doses and that the area under the curve was proportional to the dose. Steady‐state propranolol concentrations in 17 patients on regular propranolol treatment were linearly related to the dose over the range 20.640 mg d−1; the regression line extrapolated to the origin. These data indicate non‐saturable kinetics for the hepatic metabolism of propranolol within the dose ranges investigated and lead us to believe that there is no ‘oral‐threshold’ dose for propranolol. The radioimmunoassay may be useful in clinical practice for monitoring plasma propranolol concentrations and for detecting pa

ISSN:0142-2782    

DOI:10.1002/bdd.2510020106

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractAfter oral doses of 30 mg of prazepam to humans, N‐descyclopropylmethylprazepam (desalkylprazepam, N‐desmethyldiazepam) is the only major drug‐related compound in plasma. Neither the parent drug, nor its major urinary metabolites were detected in plasma. The overall concentration‐time profile of desalkylprazepamDesalkylprazepam is used as a simplified name for N‐descyclopropylmethylprazepam.in the plasma of females was lower than, and significantly different (p0.05) from those in males (342ngml−1±60 S.D.). Concentrations declined in the plasma of either sex with similar half‐lives (mean 60 h, range 37–93 h). Apparent plasma desalkylprazepam clearances were also similar (mean 1.09 1 h−1, range 0.74–1.84 1 h−1).At 12 h after the last of multiple doses of prazepam (60 mg d−1for 3 days) to lactating women, mean plasma concentrations of desalkylprazepam were 823 ng ml−1±200 S.D. and declined with a mean half‐life of about 60 h over the time‐course studied. There was only slight uptake of desalkylprazepam into blood cells; plasma : whole blood concentration ratios were constant at about 1.6. Concentrations of desalkylprazepam in milk were low at about 10 percent of the corresponding plasma levels (e.g. 86 ng ml−1±37 S.D. at 12 h). The data suggest that, expressed on a mg kg−1basis, exposed neonates could receive about 4 per cent of the matern

ISSN:0142-2782    

DOI:10.1002/bdd.2510020107

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractRats implanted with multiperforated subcutaneous plastic capsules were used as a model for study of the penetration of four cephalosporins into sites infected withEscherichia coli.The concentrations of the antibiotics were determined in uninfected and infected cages microbiologically up to 4 h after treatment. All four cephalosporins entered infected capsules faster than the control ones and the peak concentrations were attained 30–60 min earlier. The clearance of the antibiotics from infected capsules was faster than from uninfected ones, probably due to inactivation by microbial β‐lactamase(s). Serum protein binding may account for differences in the penetration rate of cephalosporins, but serum level and serum half‐time seem to contribute to their kinetic profile in tissue

ISSN:0142-2782    

DOI:10.1002/bdd.2510020108

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractConcomitant administration of antacid increased the maximum concentration (Cpmax) and the area under the plasma concentration‐time curve (AUC) of 100 mg oral dose of metoprolol by 25 per cent (p<0.05) and 11 per cent (p<0.1) respectively. For atenolol the opposite effect was observed andCpmaxand AUC were decreased by 37 and 33 per cent respectively (p<0.02). In both cases the antacid did not affect the time‐course of the drug in the plasma. Pretreatment with metoclopramide did not affect the time‐course of atenolol in the plasma or its bioavailability. Propantheline prolonged the absorption phase of atenolol and the time of peaking (tmax) was shifted from 2.1 to 4.5 h.Cpmaxof atenolol was essentially unchanged by propantheline pretreatment while the AUC was increased by 36 per cent. It is concluded that the negative effect of the antacid on the bioavailability of atenolol is caused by a reduction in thein vivodissolution rate due to increased gastric pH. The positive effect of propantheline might be due either to more efficient absorption of atenolol in the upper part of the intestine or more extensive dissolution of the drug as a result of prolonged contact with gastric juice or a combination of these fa

ISSN:0142-2782    

DOI:10.1002/bdd.2510020109

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractDistribution kinetics of gentamicin in whole blood were studied. After spiking human blood to an initial concentration of 20 μg ml−1, plasma gentamicin concentrations dropped to minima at about 5 min then increased to maxima at about 15 min and remained constant afterwards. A difference of up to 36 per cent between the maximum and minimum was found. The equilibration was faster with lower initial concentrations. These unusual distribution phenomena might be attributed to the Schiff base formation between nonprotonated amino groups of gentamicin and free fatty aldehyde groups on blood cell membrane. The mean equilibrium blood cells/plasma partition ratio was about 0.1. Similar equilibration kinetics were observed with blood of rabbits after being intravenously dosed with gentamicin. Therefore, the time elapsed between the collection and centrifugation of blood samples, especially shortly after dosing, may have a significant effect on the ‘measured’ plasma gentamicin concentration. Distribution between plasma and blood cells may also occur in a similar manner with other drugs which have primary amino groups. It is recommended that distribution kinetics of drugs and metabolites in blood be included in pharmacokinetic s

ISSN:0142-2782    

DOI:10.1002/bdd.2510020110

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510020111

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY