[Pharmacokinetic study of zidovudine in parenteral drug addicts with human immunodeficiency virus infection].

BACKGROUND

The aim of this study was to know the pharmacokinetics of zidovudine (ZDV) in steady state in patients with infection by the human immunodeficiency virus (HIV) in whom the risk factor was intravenous drug use.

METHODS

The study was carried out in 8 patients in stage IV of the Centers for Disease Control (CDC) with no acute intercurrent process, with normal liver and renal function, orally receiving 250 mg of ZDV every 6 hours. Blood samples were taken between 30 and 360 minutes from the last doses taken during fasting. Plasma concentrations of ZDV and glucuronide zidovudine (G-ZDV) were determined by radioimmunoassay with the data being adapted to a monocompartmental pharmacokinetic model.

RESULTS

The maximum concentration (Cmax) of ZDV was 0.81 +/- 0.38 microgram/ml demonstrating high interindividual variability with values between 0.35 microgram/ml and 1.45 microgram/ml. The mean Cmax of G-ZDV was 1.44 +/- 0.64 microgram/ml. The mean t1/2 of ZDV and G-ZDV was 1.63 +/- 0.75 hours and 1.12 +/- 0.32 hours, respectively, with values oscillating between 0.99 and 3.14 h in the case of ZDV. The area below the curve concentration/time (AUC) of ZDV was 1.43 +/- 0.34 microgram-h/ml and in the case of G-ZDV the AUC was 2.73 +/- 0.91 microgram-h/ml. Total body clearance (Clb) of ZDV was 2.11 +/- 0.64 l/kg/h and the volume of distribution (Vd) of ZDV was 5.6 +/- 1.73 l/kg.

CONCLUSIONS

The results of this study demonstrate that there is a marked interindividual variability in the pharmacokinetics of zidovudine suggesting the need for adapting dosage to patients weight and monitoring plasma concentration.