CLARITHROMYCIN DOES NOT AFFECT PHOSPHORYLATION OF ZIDOVUDINE IN-VITRO

Zidovudine (ZDV) and clarithromycin (CLR) are often used simultaneousl y in the management of patients with AIDS. While pharmacokinetic studi es show decreased absorption of ZDV when it is administered with CLR, it is unknown if CLR affects the intracellular metabolism of ZDV. We i nvestigated the effects of CLR on the intracellular metabolism of ZDV in vitro. CEM-T4 cells were coincubated with 1 mu M ZDV ([H-3]ZDV, 3 m u Ci/ml) either alone or with 1 or 10 mu M CLR. Cells were also grown in the presence of CLR for 48 h prior to exposure to ZDV. Samples were analyzed for mono-, di-, and triphosphate metabolites of [H-3]ZDV by high-performance liquid chromatography separation and radiochemical de tection. There were no significant differences in levels of intracellu lar metabolites of ZDV following exposure to ZDV, either alone or with 1 or 10 mu M CLR and under both coincubated and preincubated conditio ns. These results show that treatment with CLR does not alter the form ation of phosphorylated metabolites of ZDV in this cell line.