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The Effect of β-Carotene Supplementation on the Pharmacokinetics of Nelfinavir and Its Active Metabolite M8 in HIV-1-infected Patients
Faculty of Pharmacy, Universite de Montreal, C.P. 6128, succursale Centre-Ville, Montreal, H3C 3J7, Canada
Immunodeficiency Service, McGill University Health Centre, 3650 St. Urbain, Montreal, H2X 2P4, Canada
Division of Infectious Diseases, University of Ottawa at the The Ottawa Hospital/Research Institute, 501 Smyth Road, Ottawa, K1H 8L6, Canada
Office of Science Laboratory, Therapeutics Products Program, Health Canada, 0900C2, Ottawa, K1A 0K9, Canada
Faculty of Medicine, Cellular and Molecular Medicine Department, University of Ottawa, 451 Smyth Road, Room 3206, Ottawa, K1H 8M5, Canada
Agriculture and Agri-Food Canada, 93 Stone Road West, Guelph, N1G 5C9, Canada
The University of Ottawa at the Ottawa Hospital/Research Institute, 501 Smyth Road, Ottawa, K1H 8L6, Canada
Department of Pharmacy & Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Nijmegen Medical Center, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands
* Authors to whom correspondence should be addressed.
Received: 9 December 2011; in revised form: 5 January 2012 / Accepted: 6 January 2012 / Published: 12 January 2012
(This article belongs to the Special Issue Carotenoids
Abstract: β-Carotene supplements are often taken by individuals living with HIV-1. Contradictory results from in vitro studies suggest that β-carotene may inhibit or induce cytochrome P450 enzymes and transporters. The study objective was to investigate the effect of β-carotene on the steady-state pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1 infected individuals. Twelve hour nelfinavir pharmacokinetic analysis was conducted at baseline and after 28 days of β-carotene supplementation (25,000 IU twice daily). Nelfinavir and M8 concentrations were measured with validated assays. Non-compartmental methods were used to calculate the pharmacokinetic parameters. Geometric mean ratios comparing day 28 to day 1 area under the plasma concentration-time curve (AUC0–12 h), maximum (Cmax) and minimum (Cmin) concentrations of nelfinavir and M8 are presented with 90% confidence intervals. Eleven subjects completed the study and were included in the analysis. There were no significant differences in nelfinavir AUC0–12 h and Cmin (−10%, +4%) after β-carotene supplementation. The M8 Cmin was increased by 31% while the M8 AUC0–12 h and Cmax were unchanged. During the 28 day period, mean CD4+ % and CD4+:CD8+ ratio increased significantly (p < 0.01). β-carotene supplementation increased serum carotene levels but did not cause any clinically significant difference in the nelfinavir and M8 exposure.
Keywords: β-carotene; HIV; nelfinavir; interaction; pharmacokinetics
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Sheehan, N.L.; Heeswijk, R.P.G.; Foster, B.C.; Akhtar, H.; Singhal, N.; Seguin, I.; DelBalso, L.; Bourbeau, M.; Chauhan, B.M.; Boulassel, M.-R.; Burger, D.M.; Lalonde, R.G.; Cameron, D.W. The Effect of β-Carotene Supplementation on the Pharmacokinetics of Nelfinavir and Its Active Metabolite M8 in HIV-1-infected Patients. Molecules 2012, 17, 688-702.
Sheehan NL, Heeswijk RPG, Foster BC, Akhtar H, Singhal N, Seguin I, DelBalso L, Bourbeau M, Chauhan BM, Boulassel M-R, Burger DM, Lalonde RG, Cameron DW. The Effect of β-Carotene Supplementation on the Pharmacokinetics of Nelfinavir and Its Active Metabolite M8 in HIV-1-infected Patients. Molecules. 2012; 17(1):688-702.
Sheehan, Nancy L.; Heeswijk, Rolf P. G. van; Foster, Brian C.; Akhtar, Humayoun; Singhal, Neera; Seguin, Isabelle; DelBalso, Lina; Bourbeau, Marc; Chauhan, Bobby M.; Boulassel, Mohammed-Rachid; Burger, David M.; Lalonde, Richard G.; Cameron, Donald William. 2012. "The Effect of β-Carotene Supplementation on the Pharmacokinetics of Nelfinavir and Its Active Metabolite M8 in HIV-1-infected Patients." Molecules 17, no. 1: 688-702.