In humans and various animal species, 3'-azido-3'-deoxythymidine (AZT) is in part eliminated by the kidneys, where it undergoes significant tubular secretion. The goal of this project was to develop, in a continuous renal epithelial cell line (LLCPK1), a model of AZT transport in which mechanisms of drug interactions could be investigated. Transport properties of H3-AZT were studied in LLCPK1 cells grown as monolayers on permeable filters. This system provides access to the basolateral and apical surfaces of the epithelium and allows the determination of substrate transepithelial flux from the basolateral side to the apical side (B-->A/secretory direction) and apical to basolateral side (A-->B/reabsorptive direction). The B-->A flux of AZT was significantly greater than B-->A flux of mannitol (a nontransported substrate) and was temperature dependent (37 degrees C >> 4 degrees C). The AZT A-->B flux was significantly smaller than the B-->A flux, indicating that the drug is predominantly secreted in this renal epithelium. The B-->A flux was significantly inhibited by the organic bases cimetidine, quinine, quinidine, and trimethoprim. Log concentration dose studies indicate that quinine is a weak inhibitor (IC50 = 9.61 mM) of AZT B-->A flux, and that AZT is a moderate inhibitor (IC50 = 0.69 mM) of the organic base cimetidine. These results suggest that AZT may share the organic base transporter in the renal epithelium, and that this model can be used successfully to study transport properties and renal drug-drug interactions of AZT.