Pharmacokinetics of quinine in patients with chronic renal failure

Abstract

Methods: We investigated the pharmacokinetics of quinine (Qn) following administration of a single oral dose of 600 mg On sulphate in six male Thai patients with a moderate degree of chronic renal failure (CRF), and six male Thai subjects with normal renal function. Results: The drug was well tolerated in both groups of subjects; no major adverse reactions were observed. A marked alteration in the pharmacokinetics of On was found in patients with CRF compared to healthy subjects; there were six significant changes in the pharmacokinetic parameters. Absorption was delayed, but increased in CRF (t(max) 4.5 vs 1.6 h, C(max) 6.17 vs 3.45 μg ml-1). Total clearance was significantly reduced (0.94 vs 2.84 ml min-1kg-1, whereas V(z)/f remained unchanged (1.82 vs 2.78 l·kg-1). This resulted in the increased values of AUC and prolongation of the t( 1/2 z) and MRT in the patients (AUG 181.5 vs 61.8 μg min-1ml-1, t(1/2z) 26 vs 9.7 h, MRT 36.4 vs 11.3 h). Median concentrations of plasma unbound fraction of on collected at 4 h after drug administration in patients and healthy subjects were 7.3 vs 9.8%, respectively.