Hepatobiliary disposition of valproic acid and valproate glucuronide: use of a pharmacokinetic model to examine the rate-limiting steps and potential sites of drug …
CL Booth, GM Pollack, KL Brouwer - Hepatology, 1996 - journals.lww.com
Previous work in this laboratory has suggested that the nonlinear disposition of valproic acid
(VPA) in the rat may be due to nonlinear distribution of VPA into the liver. The present study
was undertaken to elucidate further the hepatobiliary disposition of VPA. VPA (0.1-2 mmol/L)
was incubated with isolated rat hepatocytes in vitro. Uptake of [3 H]-VPA was linear from 10
to 50 seconds, with minimal (< 7 percent) biotransformation. The initial velocity of VPA
uptake varied in proportion with the extracellular concentration and was temperature …
(VPA) in the rat may be due to nonlinear distribution of VPA into the liver. The present study
was undertaken to elucidate further the hepatobiliary disposition of VPA. VPA (0.1-2 mmol/L)
was incubated with isolated rat hepatocytes in vitro. Uptake of [3 H]-VPA was linear from 10
to 50 seconds, with minimal (< 7 percent) biotransformation. The initial velocity of VPA
uptake varied in proportion with the extracellular concentration and was temperature …
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