Pharmacokinetics of Co-Formulated Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate After Switch From Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Healthy Subjects

Journal of Acquired Immune Deficiency Syndromes : JAIDS
Srini RamanathanBrian P Kearney

Abstract

Elvitegravir (EVG), a HIV integrase inhibitor, is metabolized primarily by CYP3A, and secondarily by UGT1A1/3; Efavirenz (EFV), a HIV non-nucleoside reverse transcriptase inhibitor, is metabolized by Cytochrome P450 (CYP) 2B6 and induces CYP3A and uridine diphosphate glucuronosyltransferase (UGT) with residual effects post discontinuation because of long T1/2 (40-55 hours). This study evaluated the pharmacokinetics after switching from efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) to elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF). Healthy subjects (n = 32 including n = 8 CYP2B6 poor metabolizers) received EVG/COBI/FTC/TDF (150/150/200/300 mg) on days 1-7, and after a washout, received EFV/FTC/TDF (600/200/300 mg) on days 15-28 and switched to EVG/COBI/FTC/TDF (150/150/200/300 mg) for 5 weeks (days 29-62). Pharmacokinetic assessments occurred on days 7, 28, 35, and 42; trough samples (Ctrough) were collected periodically until day 63. Safety was assessed throughout the study. Twenty-nine subjects completed with 3 adverse events leading to discontinuation; no grade ≥3 adverse events were reported. Post-EFV/FTC/TDF, mean EVG area under concentration (AUCtau) was 37% and...Continue Reading

References

Aug 2, 2002·Clinical Pharmacology and Therapeutics·Stéphane MoulyPaul B Watkins
Feb 26, 2004·Antimicrobial Agents and Chemotherapy·Richard C BrundageCourtney V Fletcher
Nov 30, 2006·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Margaret A Chesney
Jul 22, 2009·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Marta BoffitoAnton Pozniak
Feb 26, 2011·Clinical Pharmacokinetics·Srinivasan RamanathanBrian P Kearney
Jul 20, 2011·The New England Journal of Medicine·Myron S CohenUNKNOWN HPTN 052 Study Team

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Citations

Jun 20, 2017·The Annals of Pharmacotherapy·Alice TsengElizabeth J Phillips
Apr 6, 2019·Expert Opinion on Drug Metabolism & Toxicology·Yuqing GongSantosh Kumar
Nov 2, 2019·Expert Opinion on Drug Metabolism & Toxicology·Dario CattaneoGiuliano Rizzardini
Jul 5, 2019·Science Translational Medicine·Corbin G ThompsonAngela D M Kashuba

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