Interactions of antineoplastic chemotherapy with zidovudine pharmacokinetics in patients with HIV-related neoplasms

To evaluate the perturbations in zidovudine (ZDV) pharmacokinetics as a consequence of antineoplastic chemotherapeutic treatments, we performed a prospective crossover study in 13 HIV-infected patients with cancer. The subjects received 2-day regimens of ZDV (250 mg x 2/day). On the first day ZDV was administered alone, whereas on the second day it was combined with antitumor chemotherapies specific for the histological type (ZDV + chemotherapy). Blood sample and urine collections were performed over a 12-hour period following oral administration of the antiretroviral agent. ZDV was measured with high-performance liquid chromatography. Pharmacokinetic parameters of ZDV were calculated by a noncompartmental model. The mean ZDV area under curve (AUC) was not significantly different in the patients treated with ZDV alone and ZDV + chemotherapy. Comparison of plasma elimination half-life (t((1/2))), apparent systemic clearance (CL/F), and apparent volume of distribution (Vd/F) of ZDV did not show any significant difference before and after chemotherapy. Conversely, some significant differences were observed for both mean peak concentration (C(max)) of ZDV and the corresponding time (T(max)). There was a 57% reduction in C(max) (p<0.05) and a 66% increase in T(max) (p<0.05) after chemotherapy compared with treatment with ZDV alone. No differences were observed in the urinary excretion of ZDV and ZDV glucuronide and urinary metabolic ratio, as a consequence of antineoplastic treatment. In conclusion, this study demonstrates that some minor perturbations in ZDV pharmacokinetics (i.e. C(max) and T(max)) derived from antineoplastic chemotherapy. Based on the observation that antineoplastic chemotherapy had no significant effect on plasma ZDV concentration expressed as AUC, the observed pharmacokinetic interaction would not warrant by itself a change in the ZDV dosage during chemotherapy.