Pharmacokinetics of Abacavir in HIV-1-Infected Patients with Impaired Renal Function

Abstract

Background: Abacavir is a potent, novel 2′-deoxyguanosine analogue reverse transcriptase inhibitor (NRTI) which effectively suppresses HIV-1 replication. To date, there is no pharmacokinetic study in patients with renal impairment. Methods: Five HIV-1-infected patients with various degrees of renal dysfunction (creatinine clearance 60, 40, 25, 20 and 1 haemodialyzed patient) were evaluated after being treated for at least 2 months with multi-antiretroviral therapy including abacavir. After an overnight fast, the subjects received their abacavir dosage (600 or 300 mg). Blood samples were withdrawn and plasma concentrations determined. A nonparametric pharmacokinetic analysis was then performed. The dialysability of abacavir was also evaluated. Results: Time of maximum plasma concentration (T_max) was constant among the subjects with a mean value of 0.7 ± 0.27 h (range 0.33–1). Maximum plasma concentration (C_max) ranged from 2.76 to 4.15 mg/l (mean 3.44 ± 0.59). The elimination half-life ranged from 1.31 to 2.67 h (mean 2.08 ± 0.51). Normalized C_max/dose ranged from 0.007 to 0.014 mg/l and normalized AUC(0-inf)/dose ranged from 0.014 to 0.035 mg·h/l. In haemodialysis the dialysance was 60–80 ml/min with a fractional drug removal of 24% during a 4-hour haemodialysis session with a high permeability membrane. Discussion: In our patients, absorption, elimination and distribution phases were not altered by renal insufficiency. Furthermore, our pharmacokinetic data are similar to those obtained in patients with normal renal function. Therefore, dosage adjustment is not necessary in patients with renal insufficiency. In haemodialyzed patients, treatment can be administered independently to the dialysis session because of the negligible elimination of abacavir in the dialysate.