Pharmacokinetics of intracellular zidovudine and its phosphorylated anabolites in the absence and presence of stavudine using an in vitro human peripheral blood mononuclear cell (PBMC) model.

Both zidovudine (ZDV) and stavudine (D4T) must be intracellularly converted to their respective active triphosphate anabolites (ZDV-TP and D4T-TP). It is hypothesized that the combination of ZDV and D4T may lead to altered formation of phosphorylated anabolites for either drug. The objective of this study was to investigate the effect of D4T on intracellular ZDV phosphorylation. Human PBMCs were incubated with [(3)H]ZDV in the presence and absence of D4T. Cells were harvested at several time points over 12 h to determine area under the intracellular concentration versus time curve (AUC) of ZDV and its phosphorylated anabolites. Radiolabled ZDV and anabolites were quantified using HPLC and LS. The AUC for ZDV-TP was 0.53 and 0.52 pmol x h/10(6) PBMC in the absence and presence of D4T, respectively. The AUC for ZDV monophosphate was 157.45 and 172.44 pmol x h/10(6) PBMC pre and post D4T. D4T does not appear to affect the formation of intracellular ZDV phosphates in human PBMCs under the conditions studied.