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  • 1
    ISSN: 1432-1041
    Keywords: Rifampicin ; induction of drug metabolism ; cirrhosis ; cholestasis ; hexobarbital kinetics ; tolbutamide kinetics ; plasma concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients with hepatic cirrhosis or cholestasis were treated with rifampicin for 7 to 132 days. Ten patients received hexobarbital (7.32 mg/kg) and five received tolbutamide (20 mg/kg) by i.v. infusion prior to and after rifampicin treatment; plasma concentrations of the two test compounds were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 624 to 262 min and that of tolbutamide from 292 to 160 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased more than two-fold and that of tolbutamide almost two-fold. The results suggest that rifampicin is able to stimulate hepatic drug metabolism in patients with liver disease. It was apparent in general that the induction did not lead to improvement of hepatocellular function during disease as judged by laboratory findings.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: hexobarbital ; cholestasis ; phenobarbital ; rifampicin ; phenytonin ; pharmackoinetics ; drug metabolism ; induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of intravenously infused hexobarbital was studied in 10 patients with intrahepatic cholestasis and in 9 with extrahepatic biliary obstruction. The results were compared with those obtained in 16 healthy young volunteers and 5 older patients with normal liver function. After infusion, the plasma concentrations showed a rapid initial decline (α-phase) and subsequently a slower decrease (β-phase). The half-life of a latter phase was 323±84 min in the healthy group, 357±151 min in the patients with intrahepatic cholestasis and 344±115 min in the group with biliary obstruction; the clearances were 3.41±0.90, 4.08±1.95 and 3.81±1.97 ml×min−1×kg−1, respectively. The differences were not statistically significant. The mean volume of the central compartment of distribution and the steady state volume of distribution were not significantly different. In two patients hexobarbital clearance during cholestasis was greater than after it had subsided. After treatment of 11 patients with cholestasis with drug metabolism-inducing agents (phenobarbital, rifampicin or phenytoin), the half-life of hexobarbital was significantly shortened and the mean value of hexobarbital clearance was more than doubled.
    Type of Medium: Electronic Resource
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