[Pharmacokinetics of zidovudine (AZT) and its metabolite (G-AZT) in healthy subjects and in patients with kidney failure].

Pharmacokinetics of zidovudine was investigated after oral administration (200 mg) in 25 HIV seronegative subjects: 14 patients with severe renal impairment (creatinine clearance 6 to 31 ml/min), 5 hemodialyzed anuric patients, and 6 healthy subjects. In healthy subjects, G. AZT concentrations are higher than those of AZT; AUC were 23.7 +/- 1.9 and 5.2 +/- 0.6 mumol.h/l respectively. Formation of G. AZT rate-limits its elimination: G. AZT half-life parallels that of AZT which is around 1 hour. In uremic patients AZT concentrations are moderately increased (AUC = 11.7 +/- 1.1 mumol.h/l), whereas half-life and MRT remains unchanged, despite the decreased renal clearance (16 +/- 2 vs 220 +/- 58 ml/min). In contrast G. AZT concentrations are markedly increased (AUC = 403 +/- 89 mumol.h/l). As a consequence of the decreased renal clearance (27 +/- 3 vs 331 +/- 42 ml/min), elimination is the rate limiting step and half-life is increased (8 +/- 2 vs 0.9 +/- 0.1 h). Contribution of a 4-hour hemodialysis session to AZT elimination appears negligible whereas elimination of G. AZT is enhanced.