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 muM) having the largest effect.
Weiss
Johanna
J
Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany. johanna.weiss@med.uni-heidelberg.de
Weis
Nicola
N
Ketabi-Kiyanvash
Nahal
N
Storch
Caroline H
CH
Haefeli
Walter E
WE
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000378:metabolism; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015658:HIV Infections; D006801:Humans; D009705:Nucleosides / Q000494:pharmacology; D009711:Nucleotides / Q000494:pharmacology; D063065:Organophosphonates / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D000068698:Tenofovir; D015854:Up-Regulation / Q000187:drug effects*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019380:Anti-HIV Agents; D009705:Nucleosides; D009711:Nucleotides; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine