[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.
Pioger
J C
JC
Taburet
A M
AM
Colin
J N
JN
Colaneri
S
S
Fillastre
J P
JP
Singlas
E
E
D000328:Adult; D001002:Anuria / Q000150:complications / Q000378:metabolism / Q000628:therapy; D005260:Female; D006679:HIV Seropositivity / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D015215:Zidovudine / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000627:therapeutic use
D015215:Zidovudine
Pharmacocinétique de la zidovudine (AZT) et de son métabolite (G.AZT) chez le sujet sain et l'insuffisant rénal.