Pharmacokinetics of tolbutamide following intravenous and oral administrations in rats with obstructive jaundice.
The pharmacokinetics of tolbutamide (TB) following intravenous and oral administration was compared between normal rats and rats with experimentally-induced obstructive jaundice (OJ). The plasma concentration-time curve of i.v. administered TB was lower in rats with OJ, in comparison with normal rats. The result of the pharmacokinetic analysis showed no change in the elimination rate constant, but a significant increase in the volume of distribution in the OJ state. The increase in the volume of distribution of TB could be explained by the decreased protein binding in plasma. In the case of oral administration, the elevation of the plasma concentration was slow and the plasma concentration profile was remarkably low in rats with OJ. The rate of TB disappearance from the small-intestinal lumen was delayed in the OJ state, and its marked accumulation in the tissues of the small intestine and the liver was observed. This retarded uptake by the small-intestinal mucosa and subsequent pre-systemic accumulation might, at least in part, be the reason for the slow appearance in the systemic plasma in the OJ state.
Yamao
T
T
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Nakagami
H
H
Furuhama
K
K
Onodera
T
T
Kurosaki
Y
Y
Nakayama
T
T
Kimura
T
T
D000284:Administration, Oral; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002779:Cholestasis / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000008:administration & dosage / Q000493:pharmacokinetics*
D001798:Blood Proteins; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide