Comparative Pharmacokinetics of Zidovudine and Its Toxic Catabolite 3′-Amino-3′-Deoxythymidine in HIV-Infected Patients

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Abstract
The plasma pharmacokinetics of zidovudine (ZDV, 3′-azido-3′-deoxythymidine) and its toxic catabolite 3′-amino-3′-deoxythymidine (AMT) was investigated in six HIV-infected patients receiving 100 or 500 mg of ZDV by oral administration. Zidovudine plasma pharmacokinetic parameters were in good agreement with previously reported data with a total plasma clearance (Cl) of 2.33 and 2.49 liters/hr/kg and an apparent elimination t½ of 1.14 and 1.20 hr at 100- and 500-mg doses, respectively. 3′-Amino-3′-deoxythymidine was detectable in the plasma of all patients, with maximum plasma levels (Cmax) being reached within 2 hr post-dosing. No dose relationship in the formation of AMT expressed as the area under the plasma level–time curve (AUC) was established within the studied dose range of ZDV. The AUCAMT was 145.4 and 92.4 ng/ml · hr after administration of 100 and 500 mg of ZDV, respectively. These results reflect an unexpectedly large interindividual variation in the formation of AMT. The lack of linearity in AMT pharmacokinetics prevents the prediction of its plasma levels based only on the administered oral dose of ZDV.

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