Influence of chronic hepatic failure on disposition kinetics of valproate excretion through a phase II reaction in rats treated with carbon tetrachloride.

Influence of chronic hepatic failure on disposition kinetics of valproate excretion through a phase II reaction in rats treated with carbon tetrachloride. Research Abstract Details 

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Influence of chronic hepatic failure on disposition kinetics of valproate excretion through a phase II reaction in rats treated with carbon tetrachloride. Abstract Text:

Phisit Khemawoot,Chiharu Maruyama,Hirotaka Tsukada,Hiroyo Noda,Junko Ishizaki,Koichi Yokogawa,Ken-ichi Miyamoto,Phisit Khemawoot,Chiharu Maruyama,Hirotaka Tsukada,Hiroyo Noda,Junko Ishizaki,Koichi Yokogawa,Ken-ichi Miyamoto,

The influence of chronic hepatic failure on the disposition kinetics of valproate (VPA) excretion via a phase II reaction was examined in rats treated with carbon tetrachloride (1.0 mg/kg, s.c., 3 times a week) for 2 or 3 months. There was no significant difference in the plasma concentration-time courses of VPA among the control and two treated groups up to 120 min after i.v. administration of VPA (75 mg/kg), but subsequently the plasma concentrations of the treated groups declined significantly below the control levels. Expression of Mrp2 mRNA in the liver of the treated groups was significantly lower than in the control group; conversely that in the kidney was significantly higher. The enzyme activity of UGTs in the liver of the treated groups decreased significantly, but UGT1A8 mRNA expression in the duodenum was increased about 3-fold. Cumulative excretion of VPA glucuronide (VPA-G) in bile of the treated groups was reduced significantly, while that in urine was markedly increased. In conclusion, the area under the VPA plasma concentration-time curve was decreased significantly in rats with chronic hepatic failure owing to increased excretion of VPA-G via the kidney as a result of induction of Mrp2, and inhibition of enterohepatic circulation of VPA-G.

Influence of chronic hepatic failure on disposition kinetics of valproate excretion through a phase II reaction in rats treated with carbon tetrachloride. Publishing Authors By Initials

P Khemawoot,C Maruyama,H Tsukada,H Noda,J Ishizaki,K Yokogawa,K Miyamoto,P Khemawoot,C Maruyama,H Tsukada,H Noda,J Ishizaki,K Yokogawa,K Miyamoto,

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Influence of chronic hepatic failure on disposition kinetics of valproate excretion through a phase II reaction in rats treated with carbon tetrachloride. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Biopharmaceutics & drug disposition

VOLUME: 28

Page Numbers: 331-8

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ISSN: 0142-2782

DAY: 21

MONTH: Sep

YEAR: 2007

Influence of chronic hepatic failure on disposition kinetics of valproate excretion through a phase II reaction in rats treated with carbon tetrachloride. Information

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LANGUAGE: eng

NlmUniqueID: 7911226

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Grant and Affiliation Information for Influence of chronic hepatic failure on disposition kinetics of valproate excretion through a phase II reaction in rats treated with carbon tetrachloride.

AFFILIATION: Department of Medicinal Informatics, Division of Cardiovascular Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Japan.

Country: England

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MEDLINETA: Biopharm Drug Dispos

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