BACKGROUND/AIMS Efflux transporters in the ATP binding cassette (ABC) superfamily have been implicated in multidrug resistance (MDR). Characterization of ABC transporters at the site of drug action is essential to overcoming MDR. In the current study, we examined the expression of seven ABC transporters in humanPBMCs in response to administration of the HIV protease inhibitors atazanavir (ATZ) and saquinavir (SQV). METHODS Fourteen healthy volunteers received 1500 mg SQV and 200 mg ATZ orally twice daily for 11 days. PBMCs were isolated from each subject at baseline and on the 11th day of treatment. Quantitative RT-PCR was used to measure PBMC expression of ABCB1, ABCC1, ABCC2, ABCC3, ABCC4, ABCC6, and ABCG2. RESULTS Preliminary results show an overall increase in ABCB1 mRNA expression following SQV-ATZ administration. Interestingly, 86% of subjects demonstrated an increase in ABCB1 mRNA expression, while the remaining subjects exhibited a decrease. The effect of SQV-ATZ treatment on mRNA expression of ABCC1, ABCC2, ABCC3, ABCC4, ABCC6, and ABCG2 was variable, with induction of any gene observed in no more than 63% of individuals. (Table) Effect of SQV-ATZ administration on ABCB1 mRNA expression ABCB1 expression change N Mean change (%) Range (%) P-value Upregulated 12 55 1 to 131 <0.01 Downregulated 2 −33 −51 and −7 <0.05 Total 14 36 −51 to 131 <0.05 CONCLUSIONS Coadministration of the HIV protease inhibitors SQV and ATZ induced ABCB1 mRNA expression in the majority of individuals tested. The effect of this induction on P-glycoprotein function is being assessed. The variability in response to treatment may be due to genetic differences in these ABC genes or their regulatory partners. Clinical Pharmacology & Therapeutics (2005) 79, P6–P6; doi: 10.1016/j.clpt.2005.12.017