摘要:

AbstractAn assay was developed for benzthiazide in plasma, urine and feces, using high performance liquid chromatography (HPLC). A reverse‐phase column was employed, with quantitation at 280 nm, using polythiazide as an internal standard. In three of four human subjects who received a 50 mg benzthiazide tablet the plasma concentrations were below the 10 ng ml−1sensitivity limit of the assay, and the urinary recovery averaged less than one per cent of the dose. One subject received a 50 mg dose as both a tablet and a solution; the urinary recoveries for these two doses were 1.7 and 10.4 per cent, respectively. Fecal samples, obtained from two subjects who received 50 mg tablets, were estimated to contain approximately 80 per cent of the administered d

ISSN:0142-2782    

DOI:10.1002/bdd.2510030102

出版商:John Wiley&Sons, Ltd.    

年代:1982

数据来源: WILEY

摘要:

AbstractA specific, sensitive, rapid, and reproducible method for iprindole in human plasma was developed using gas chromatography with trimipramine as internal standard. The sensitivity of the method is of S ng ml−1and a linearity was obtained for concentrations ranging from 12.5ngml−1to 100ngml−1with a regression coefficient of 0.9872. The plasma levels of iprindole were determined in five healthy volunteers following the administration of a single oral dose of 60 mg and in four patients admitted for endogenous depression after a 3‐week administration of 90mgd−1. Following a single oral dose to healthy volunteers, the maximum concentrations occurred between 2 and 4h after administration of the drug and the mean half‐life value was 52.5 h. In patients the steady‐state concentrations of iprindole ranged between 18

ISSN:0142-2782    

DOI:10.1002/bdd.2510030103

出版商:John Wiley&Sons, Ltd.    

年代:1982

数据来源: WILEY

摘要:

AbstractCyclobenzaprine hydrochloride was administered to healthy volunteers as a 10mg oral tablet, 10mg and 20mg intramuscular injections, and a 10mg intravenous injection. Urinary excretion and plasma level data for cyclobenzaprine together provide evidence for route dependent biotransformation. Urinary excretion of total cyclobenzaprine (unchanged plus the glucuronide conjugate) was greater for the oral treatment than for the parenteral treatments (i.m. and i.v.). Area under the plasma concentration‐time curve for unchanged cyclobenzaprine, however, was less for the oral treatment than for the parenteral treatments. Based on area calculations, the bioavailability of the 10 mg oral tablet, 10 mg i.m. and 20 mg i.m. injection was 0.33, 0.76, and 0.56, respectively, when compared to the 10mg i.v. injection of cyclobenzaprine hydrochloride. The four treatments were well tolerated and no clinically adverse effects were observe

ISSN:0142-2782    

DOI:10.1002/bdd.2510030104

出版商:John Wiley&Sons, Ltd.    

年代:1982

数据来源: WILEY

摘要:

AbstractThree healthy male subjects received single 100mg oral doses of carprofen containing 20 μCi of14C‐carprofen. Venous blood samples were drawn during the first 48 h after the dose and urine and feces were collected for 120h. Concentrations of carprofen and its metabolites in body fluids were determined by TLC and mass spectral analysis. After a lag time of 0.3±0.41h (mean ±S.D.), carprofen was absorbed rapidly and peak concentrations in the plasma were reached in 2.7 ± 1.3 h. The14C plasma concentrations declined in a biphasic fashion. The mean half‐lives of the initial (α) and terminal (β) phases were 1.1 h and 20.6 ± 6.1 h, respectively. Biotransformation to a glucuronide metabolite appeared to be the major mechanism of carprofen clearance. In 48 h 74.0 per cent of administered radioactivity was recovered in urine and 14.1 per cent was recovered in feces. A glucuronide of carprofen comprised 85.0 per cent of the radiolabelled compounds in urine. The remaining radioactivity was comprised of parent drug (12.0 per cent) and un unidentified acid‐labile conjugate of the parent drug (3.0 per cent). This pattern of metabolism and excretion is different from that in the dog and rat and may explain species differences in drug activity

ISSN:0142-2782    

DOI:10.1002/bdd.2510030105

出版商:John Wiley&Sons, Ltd.    

年代:1982

数据来源: WILEY

摘要:

AbstractThree indices of drug metabolism, antipyrine clearancein vivo, and aminopyrine N‐demethylase and bilirubin UDP‐glucuronyl transferase activity in liver biopsies, were studied in fifteen patients with amoebic liver abscess (with and without jaundice). The mean (± S.E.) antipyrine half‐life in patients with jaundice was 21.64 (±1.52)h and in patients without jaundice was 19.36 ( ± 0.93)h. It was significantly prolonged in both groups of patients as compared to controls (11.63 ± 0.86 h). It showed a good correlation with serum albumin (p<0.01), prothrombin time index (p<0.01), and aminopyrine N‐demethylase (p<0.05). Aminopyrine N‐demethylase was found to be decreased in patients without jaundice but no significant change could be observed in patients with jaundice. Bilrubin UDP‐glucuronyl transferase showed no significant change in eithe

ISSN:0142-2782    

DOI:10.1002/bdd.2510030106

出版商:John Wiley&Sons, Ltd.    

年代:1982

数据来源: WILEY

摘要:

AbstractThe effect of hydralazine on the pharmacokinetics of metoprolol, nadolol, and acebutolol has been studied by measuring drug concentrations in plasma, serum, and urine. Metoprolol is affected by hydralazine, the AUC andCmaxbeing significantly increased. The kinetics of acebutolol and its major metabolite, diacetolol, are unaffected. Poor absorption of the polar beta blocker, nadolol, does not allow a firm conclusion to be drawn regarding the effect of hydralazine. It is concluded that only beta blockers with a substantial first‐pass loss are likely to be significantly affected by hydralazin

ISSN:0142-2782    

DOI:10.1002/bdd.2510030107

出版商:John Wiley&Sons, Ltd.    

年代:1982

数据来源: WILEY

摘要:

AbstractExperiments have been carried out in dogs and man to determine the effect of hydrochlorothiazide (HCT) on the pharmacokinetics of propranlol and to evaluate the bioavailability of two dosage forms containing both propranolol and HCT (40/25 and 80/25 mg, respectively). In adult male beagles, 50 mg of HCT had no apparent effect on AUC, Cmax,Tmax, andT1/2of propranolol administered concurrently. In man, INDERIDE® (40/25 mg) and INDERIDE® (80/25 mg) were shown to be similar in bioavailability to the reference formulations, i.e. the same amount of drugs administered as the separate tablets of INDERAL® plus HYDRODIURI

ISSN:0142-2782    

DOI:10.1002/bdd.2510030108

出版商:John Wiley&Sons, Ltd.    

年代:1982

数据来源: WILEY

摘要:

AbstractThe bioavailability of an improved formulation of enteric‐coated phenylbutazone with faster dissolution, more consistentin vitrorate of drug release and improved stability was compared in 8 normal subjects at doses of 100 and 200 mg with commercially available Butacote®. Phenylbutazone was more rapidly absorbed from the new formulation and higher plasma concentrations were achieved at shorter intervals after dosing.Drug elimination rate was unaffected by reformulation and despite faster absorption the total amounts of drug reaching the circulation from the new and commercial products were similar. It was concluded that replacing Butacote® by the new formulation would provide the same therapeutic bene

ISSN:0142-2782    

DOI:10.1002/bdd.2510030109

出版商:John Wiley&Sons, Ltd.    

年代:1982

数据来源: WILEY

摘要:

AbstractPlasma acetazolamide concentrations were determined enzymatically after administration of three tablet dosage forms and a reference solution to 12 human subjects in a crossover study. Two of the tablet products represented different lots from the same manufacturer. There were no significant differences in area under the plasma level‐time curves among the four treatments. However, significant differences were found among tablets in terms of peak plasma concentration and time to reach peak concentration. These apparent differences in rate of absorption were correlated within vitrodissolution data obtained in pH 1.5 dissolution mediu

ISSN:0142-2782    

DOI:10.1002/bdd.2510030110

出版商:John Wiley&Sons, Ltd.    

年代:1982

数据来源: WILEY

摘要:

AbstractThe incidence of nephrotoxicity has been studied in 175 patients who received either gentamicin or tobramycin. All patients received individualized dosing regimens of the drugs based on pharmacokinetic parameters measured after the initial dose. Subsequent doses were calculated from the pharmacokinetic data to produce peak aminoglycoside levels of between 6 and 8 μg ml−1and trough levels that were below 2 μg ml−1. Renal toxicity was defined as a 30 per cent or greater increase in the serum creatinine level above the baseline value. Five of the 125 patients (4 per cent) who received gentamicin, and 1 of the 39 patients (2.6 per cent) who received tobramycin developed signs of nephrotoxicity. This difference was not statistically signif

ISSN:0142-2782    

DOI:10.1002/bdd.2510030111

出版商:John Wiley&Sons, Ltd.    

年代:1982

数据来源: WILEY