Pharmacokinetics of abacavir in HIV-1-infected patients with impaired renal function

Background: Abacavir is a potent, novel 2'-deoxyguanosine analogue reverse transcriptase inhibitor (NRTI) which effectively suppresses HIV-1 replicati on. To date, there is no pharmacokinetic study in patients with renal impai rment. Methods: Five HIV-1-infected patients with various degrees of renal dysfunction (creatinine clearance 60, 40, 25, 20 and 1 haemodialyzed patien t) were evaluated after being treated for at least 2 months with multi-anti retroviral therapy including abacavir. After an overnight fast, the subject s received their abacavir dosage (600 or 300 mg). Blood samples were withdr awn and plasma concentrations determined. A nonparametric pharmacokinetic a nalysis was then performed. The dialysability of abacavir was also evaluate d. 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 p lasma 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 A UC(0-inf)/dose ranged from 0.014 to 0.035 mg.h/l. In haemodialysis the dial ysance was 60-80 ml/min with a fractional drug removal of 24% during a 4-ho ur haemodialysis session with a high permeability membrane. Discussion: In our patients, absorption, elimination and distribution phases were not alte red by renal insufficiency. Furthermore, our pharmacokinetic data are simil ar to those obtained in patients with normal renal function. Therefore, dos age adjustment is not necessary in patients with renal insufficiency. In ha emodialyzed patients, treatment can be administered independently to the di alysis session because of the negligible elimination of abacavir in the dia lysate. Copyright (C) 2001 S. Karger AG, Basel.