Comparison of the induction of P-glycoprotein activity by nucleotide, nucleoside, and non-nucleoside reverse transcriptase inhibitors

Combination therapy against human immunodeficiency virus (HIV)-infection is complicated by drug–drug interactions between antiretrovirals and also between anti-HIV drugs and drugs used to treat co-morbidity. P-glycoprotein represents one important site for drug interactions and induction of its function could reduce the effectiveness of drugs that are P-glycoprotein substrates. We therefore investigated induction of P-glycoprotein function in LS180 cells by non-nucleoside and nucleoside reverse transcriptase inhibitors (NNRTIs and NRTIs) and tenofovir as essential components of antiretroviral combination therapy. P-glycoprotein activity was increased by all NNRTIs and some NRTIs with delavirdine (5.3-fold at 100 μM) having the largest effect.