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Pharmacokinetics of cobicistat boosted-elvitegravir administered in combination with rosuvastatin.
J Clin Pharmacol. 2014 Jun; 54(6):649-56.JC

Abstract

Statins are commonly used medications by HIV-1 patients. Elvitegravir/cobicistat/emtricitabine/tenofovir DF is a single tablet regimen for the treatment of HIV. The pharmacokinetic interaction between cobicistat-boosted elvitegravir (EVG/co) and rosuvastatin was evaluated. Breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 1B1 and 1B3 inhibition were assessed in vitro. Healthy subjects (N = 12) received a single dose of rosuvastatin 10 mg alone and in combination with EVG/co. Intensive pharmacokinetic sampling was conducted and safety was assessed throughout the study. Rosuvastatin pharmacokinetic exposure parameters were evaluated using 90% confidence intervals (CI) of the geometric mean ratio (GMR) of the test (combination) versus reference (rosuvastatin alone) using equivalence boundaries of 70-143% for AUCinf and 70-175% for Cmax . Elvitegravir and cobicistat inhibited BCRP and OATP in vitro, emtricitabine and TDF did not. Clinically, study treatments were well tolerated, with adverse events generally mild. Upon coadministration, rosuvastatin plasma concentrations increased (Cmax 89% higher), while AUCinf changes were modest (38% higher) and clinically nonrelevant, potentially driven by moderate inhibition of intestinal efflux by BCRP, and/or hepatic uptake by OATPs by EVG/co. Elvitegravir and cobicistat pharmacokinetics were comparable to historical data. Rosuvastatin may be coadministered with EVG/COBI/FTC/TDF without dose adjustment.

Authors+Show Affiliations

Gilead Sciences, Inc., Foster City, CA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24375014

Citation

Custodio, Joseph M., et al. "Pharmacokinetics of Cobicistat Boosted-elvitegravir Administered in Combination With Rosuvastatin." Journal of Clinical Pharmacology, vol. 54, no. 6, 2014, pp. 649-56.
Custodio JM, Wang H, Hao J, et al. Pharmacokinetics of cobicistat boosted-elvitegravir administered in combination with rosuvastatin. J Clin Pharmacol. 2014;54(6):649-56.
Custodio, J. M., Wang, H., Hao, J., Lepist, E. I., Ray, A. S., Andrews, J., Ling, K. H., Cheng, A., Kearney, B. P., & Ramanathan, S. (2014). Pharmacokinetics of cobicistat boosted-elvitegravir administered in combination with rosuvastatin. Journal of Clinical Pharmacology, 54(6), 649-56. https://doi.org/10.1002/jcph.256
Custodio JM, et al. Pharmacokinetics of Cobicistat Boosted-elvitegravir Administered in Combination With Rosuvastatin. J Clin Pharmacol. 2014;54(6):649-56. PubMed PMID: 24375014.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics of cobicistat boosted-elvitegravir administered in combination with rosuvastatin. AU - Custodio,Joseph M, AU - Wang,Hui, AU - Hao,Jia, AU - Lepist,Eve-Irene, AU - Ray,Adrian S, AU - Andrews,Jessica, AU - Ling,Kah Hiing J, AU - Cheng,Andrew, AU - Kearney,Brian P, AU - Ramanathan,Srinivasan, Y1 - 2014/01/17/ PY - 2013/09/15/received PY - 2013/12/20/accepted PY - 2013/12/31/entrez PY - 2014/1/1/pubmed PY - 2014/12/30/medline KW - Stribild™ KW - breast cancer resistance protein KW - elvitegravir KW - organic anion transporting polypeptide KW - pharmacokinetics KW - statins SP - 649 EP - 56 JF - Journal of clinical pharmacology JO - J Clin Pharmacol VL - 54 IS - 6 N2 - Statins are commonly used medications by HIV-1 patients. Elvitegravir/cobicistat/emtricitabine/tenofovir DF is a single tablet regimen for the treatment of HIV. The pharmacokinetic interaction between cobicistat-boosted elvitegravir (EVG/co) and rosuvastatin was evaluated. Breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 1B1 and 1B3 inhibition were assessed in vitro. Healthy subjects (N = 12) received a single dose of rosuvastatin 10 mg alone and in combination with EVG/co. Intensive pharmacokinetic sampling was conducted and safety was assessed throughout the study. Rosuvastatin pharmacokinetic exposure parameters were evaluated using 90% confidence intervals (CI) of the geometric mean ratio (GMR) of the test (combination) versus reference (rosuvastatin alone) using equivalence boundaries of 70-143% for AUCinf and 70-175% for Cmax . Elvitegravir and cobicistat inhibited BCRP and OATP in vitro, emtricitabine and TDF did not. Clinically, study treatments were well tolerated, with adverse events generally mild. Upon coadministration, rosuvastatin plasma concentrations increased (Cmax 89% higher), while AUCinf changes were modest (38% higher) and clinically nonrelevant, potentially driven by moderate inhibition of intestinal efflux by BCRP, and/or hepatic uptake by OATPs by EVG/co. Elvitegravir and cobicistat pharmacokinetics were comparable to historical data. Rosuvastatin may be coadministered with EVG/COBI/FTC/TDF without dose adjustment. SN - 1552-4604 UR - https://www.unboundmedicine.com/medline/citation/24375014/Pharmacokinetics_of_cobicistat_boosted_elvitegravir_administered_in_combination_with_rosuvastatin_ L2 - https://doi.org/10.1002/jcph.256 DB - PRIME DP - Unbound Medicine ER -