摘要:

Clinical Pharmacology and Therapeutics(1990)48, 603–605; doi:10.1038/clpt.1990.2

ISSN:0009-9236    

DOI:10.1038/clpt.1990.200

年代:1990

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1990)48, 606–610; doi:10.1038/clpt.1990.2

ISSN:0009-9236    

DOI:10.1038/clpt.1990.201

年代:1990

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1990)48, 611–612; doi:10.1038/clpt.1990.2

ISSN:0009-9236    

DOI:10.1038/clpt.1990.202

年代:1990

数据来源: WILEY

摘要:

The pharmacokinetics of morphine was studied in six patients in whom a radiologic localization of an insulinoma was to be performed under general anesthesia. Sampling was done in the peripheral artery, the mesenteric vein in five of the six patients, the hepatic vein, and the peripheral vein, as well as in urine. Hepatic blood flow was estimated by an indocyanine green infusion technique at the end of the radiologic procedure. Morphine terminal half‐life was 92 ± 9 minutes, total body clearance was 1260 ml · min−1, and the hepatic extraction ratio was 0.65 ± 0.11. No concentration gradient was observed between the artery and the superior mesenteric vein, showing that no gut wall metabolism of morphine occurred. The total body clearance exceeded the hepatic clearance by 38%. It was concluded that the extrahepatic extraintestinal clearance of morphine probably occurred through the kidney.Clinical Pharmacology and Therapeutics(1990)48, 613–618; doi:10.1038/clpt

ISSN:0009-9236    

DOI:10.1038/clpt.1990.203

年代:1990

数据来源: WILEY

摘要:

The relative importance ofN‐hydroxylation and acetylation of dapsone to the oral clearance of dapsone (100 mg) was investigated in seven healthy volunteers. Plasma dapsone and monoacetyldapsone concentrations rose rapidly with subsequent similar monoexponential elimination. The oral clearance of dapsone was low (33 ± 14 ml/min), with a threefold variability. Four subjects were identified as fast acetylators; however, differences in acetylation did not explain the variability in oral clearance. The cumulative urinary recoveries of dapsone and its hydroxylamine were approximately 20% of the dose. The formation clearance of hydroxylamine, which exhibited a tenfold intersubject variability, was closely associated with the oral clearance of dapsone (r= 0.96). Thus, the formation of the hydroxylamine is more important than acetylation in determining dapsone's intersubject variability in oral clearance. Variation inN‐hydroxylation may have clinical consequences, because the hydroxylamine is considered to be important in dapsone‐mediated toxicity.Clinical Pharmacology and Therapeutics(1990)48, 619–627; doi:10.1038/clpt

ISSN:0009-9236    

DOI:10.1038/clpt.1990.204

年代:1990

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1990)48, 627–627; doi:10.1038/clpt.1990.2

ISSN:0009-9236    

DOI:10.1038/clpt.1990.205

年代:1990

数据来源: WILEY

摘要:

The pharmacokinetics of the sulfonamide‐type diuretic xipamide was studied in patients with liver cirrhosis and ascites and compared with healthy control subjects. After oral administration of 40 mg xipamide, the diuretic was rapidly distributed in the blood and the ascites. The ratio of the area under the concentration‐time curve (AUC) of plasma and ascitic fluid was 7:2, as was the protein content in the respective compartments. The AUC in plasma of cirrhotic patients was significantly greater than in control subjects (p<0.001). The most striking finding was the increase of the amount (Ae) of parent drug and main metabolite excreted into the urine (p<0.001). The renal clearance of xipamide was only moderately reduced in patients with liver cirrhosis. Both AUC and Ae were positively correlated to the plasma concentration of direct bilirubin of the patients (p<0.05). We concluded that nonrenal drug clearance in patients with liver cirrhosis was reduced as a result of the blockade of hepatobiliary excretion during cholestatic conditions.Clinical Pharmacology and Therapeutics(1990)48, 628–632; doi:10.1038/clpt.19

ISSN:0009-9236    

DOI:10.1038/clpt.1990.206

年代:1990

数据来源: WILEY

摘要:

In this clinical investigation, four groups of subjects (eight young women and eight young men [age range, 18 to 25 years], and eight elderly women and eight elderly men [>60 years of age]) received single oral doses (400 mg) of racemic mephobarbital. The apparent total body clearance ofR‐mephobarbital was much greater and the elimination half‐life was much shorter in the young men compared with the other three groups. This enantiomer displayed an age‐dependent gender effect and a gender‐dependent age effect in its metaoblism. The apparent total body clearance of theS‐enantiomer was much lower than that of theR‐enantiomer in all subjects and did not differ between subject groups, although the elimination half‐life was slightly but signifiantly shorter in young males. A consequence of these enantiomeric differences was an apparently enhanced stereoselectivity in the metabolism of mephobarbital in young men. These substantial influences of age and gender on the stereoselective disposition of mephobarbital are consistent with recent findings concerning the expression and regulation of cytochrome P450 enzymes.Clinical Pharmacology and Therapeutics(1990)48, 633–640; doi:10.10

ISSN:0009-9236    

DOI:10.1038/clpt.1990.207

年代:1990

数据来源: WILEY

摘要:

The disposition of a single intravenous dose of14C‐nicotine was investigated in six cigarette smokers and six nonsmokers. Plasma and urinary elimination of both nicotine and cotinine was faster in smokers than in nonsmokers. In the urine of both smokers and nonsmokers, we identified nicotine and eight metabolites, including two new metabolites: metabolite A (3‐hydroxycotinine glucuronide) and metabolite G (demethylcotinine Δ2′,3′‐enamine). Metabolites A and G were of particular interest because, in smokers, they both persisted longer than cotinine. This property renders them more sensitive than cotinine as potential indicators of passive exposure to cigarette smoke.Clinical Pharmacology and Therapeutics(1990)48, 641–651; doi:10.1038/

ISSN:0009-9236    

DOI:10.1038/clpt.1990.208

年代:1990

数据来源: WILEY

摘要:

The tolerance, pharmacokinetics, and pharmacodynamics of adinazolam andN‐desmethyladinazolam (NDMAD) were assessed after single oral doses of 10, 30, and 50 mg adinazolam mesylate, NDMAD mesylate, and placebo. Within doses, six healthy male volunteers received these treatments in a double‐blind crossover design. No clinically significant changes were observed in blood pressure, pulse, respiration, or clinical laboratory test results. Untoward effects were typical of benzodiazepines. Adinazolam and NDMAD kinetics were dose independent. Greater than 95% of the adinazolam dose was metabolized to NDMAD. Adinazolam and NDMAD mesylate produced dose‐related increases in uric acid clearance and deceases in plasma uric acid. Both adinazolam and NDMAD mesylate administration resulted in dose‐related sedation and decrements in psychomotor performance. Within doses, decrements produced by adinazolam and NDMAD were quantitatively similar. These results suggest that both adinazolam and NDMAD possess uricosuric activity and support the hypothesis that NDMAD primarily mediates benzodiazepine‐like effects of adinazolam mesylate.Clinical Pharmacology and Therapeutics(1990)48, 652–664; doi:10.1038/c

ISSN:0009-9236    

DOI:10.1038/clpt.1990.209

年代:1990

数据来源: WILEY