Pharmacokinetics of Tenofovir Alafenamide When Coadministered With Other HIV Antiretrovirals.
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Begley R, Das M, Zhong L, Ling J, Kearney BP, Custodio JM
Pharmacokinetics of Tenofovir Alafenamide When Coadministered With Other HIV Antiretrovirals.
J Acquir Immune Defic Syndr. 2018 Aug 1;78(4):465-472. doi: 10.1097/QAI.0000000000001699.
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- 29649076 [ View in PubMed]
- Abstract
BACKGROUND: Tenofovir alafenamide (TAF), a prodrug of the nucleotide analogue tenofovir (TFV), is an antiretroviral (ARV) agent approved either as a complete regimen [elvitegravir/cobicistat/emtricitabine (F)/TAF, rilpivirine/F/TAF, bictegravir/F/TAF], or for use with other ARVs (F/TAF), for treatment of HIV. TAF is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters. Disposition of TAF may be altered by comedications that can inhibit or induce P-gp or BCRP transporters. The effects of ARVs on the pharmacokinetics of TAF were evaluated in 3 studies. METHODS: Healthy participants received TAF administered alone or with rilpivirine in study 1, with dolutegravir, ritonavir-boosted atazanavir (ATV + RTV), lopinavir (LPV/RTV), or darunavir (DRV + RTV) in study 2, and with the pharmacokinetic enhancer cobicistat or efavirenz in study 3. RESULTS: Across the 3 studies, 98 participants received treatment with TAF and a coadministered agent (n = 10-34/cohort). All study treatments were well tolerated. TAF and TFV exposures were unaffected after co-administration with rilpivirine and dolutegravir. Coadministration with P-gp/BCRP inhibitors such as cobicistat or PI-based regimens (ATV + RTV, LPV/r, or DRV + RTV) resulted in a range of 6%-183% increases in TAF and 105%-316% increases in TFV exposure, whereas coadministration with a P-gp inducer, efavirenz, resulted in a 15%-24% decrease in TAF and TFV exposure. CONCLUSIONS: Evaluation of the drug interaction between TAF and other commonly prescribed boosted and unboosted ARVs provides characterization of the susceptibility of TAF and/or TFV pharmacokinetics to inhibitors or inducers of P-gp/BCRP transporters.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Tenofovir P-glycoprotein 1 Protein Humans NoSubstrateDetails Tenofovir alafenamide P-glycoprotein 1 Protein Humans UnknownSubstrateDetails