Liver Fibrosis Stages Affect Organic Cation Transporter 1/2 Activities in Hepatitis C Virus-Infected Patients.

This study aims to evaluate the impact of liver fibrosis stages of chronic infection with hepatitis C virus (HCV) on the in vivo activity of organic cation transporters (hepatic OCT1 and renal OCT2) using metformin (MET) as a probe drug. Participants allocated in Group 1 ( = 15, mild to moderate liver fibrosis) or 2 ( = 13, advanced liver fibrosis and cirrhosis) received a single MET 50 mg oral dose before direct-acting antiviral (DAA) drug treatment (Phase 1) and 30 days after achieving sustained virologic response (Phase 2). OCT1/2 activity (MET AUC) was found to be reduced by 25% when comparing the two groups in Phase 2 (ratio 0.

Clinical treatment for hepatitis C reverses CYP2C19 inhibition.

Aims: Infection by the hepatitis C virus (HCV) generates inflammatory response selectively modulating cytochrome P450 protein (CYP) activities. This study assessed the effect of chronic hepatitis C on CYP2C19 activity in patients with HCV.

Methods: Patients with HCV infection (n = 23) at different fibrosis stages were allocated into groups 1 (F0/F1 and F2, mild to moderate fibrosis) and 2 (F3 and F4, advanced fibrosis stages).

Therapeutic Doses of Eltrombopag do not Inhibit Hepatic BCRP in Healthy Volunteers: Intravenous Ceftriaxone as a Model.

Purpose: Ceftriaxone elimination occurs through breast cancer resistance transporter (BCRP) and multidrug resistance-associated protein 2 (MRP-2) which are expressed on the canalicular membrane of hepatocytes. Eltrombopag, a thrombopoetin receptor agonist used in the treatment of immune thrombocytopenic purpura, is reported in in vitro studies as an inhibitor of intestinal BCRP but not an inhibitor of hepatic BCRP. Thus, the present study evaluates the effect of therapeutic doses of eltrombopag on the clinical pharmacokinetics of intravenous ceftriaxone.

An indirect stereoselective analysis of nebivolol glucuronides in plasma by LC-MS/MS: Application to clinical pharmacokinetics.

Nebivolol is a racemate of the d-isomer responsible for β adrenergic receptor antagonism and the l-isomer responsible for the release of nitric oxide from endothelial cells. Nebivolol is mainly metabolized to nebivolol glucuronide, which also contribute to the nebivolol β adrenoreceptor antagonism. This study reports the development and validation of an indirect stereoselective method of analysis of nebivolol glucuronides in plasma by LC-MS/MS.

Stereoselective analysis of nebivolol isomers in human plasma by high-performance liquid chromatography-tandem mass spectrometry: application in pharmacokinetics.

Nebivolol is available for clinical use as a racemic mixture. Isomer d-nebivolol (SRRR) is a β1 adrenergic receptor blocker and its antipode, l-nebivolol (RSSS) is responsible for endothelium-dependent NO liberation. This report describes the development and validation of a method of analysis of nebivolol isomers in human plasma by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS).