title: The effect of β-carotene supplementation on the pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1-infected patients.
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 (AUC(0-12 h)), maximum (C(max)) and minimum (C(min)) 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 AUC(0-12 h) and C(min) (-10%, +4%) after β-carotene supplementation. The M8 C(min) was increased by 31% while the M8 AUC(0-12 h) and C(max) 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.
authors.affiliation: Faculty of Pharmacy, Universite de Montreal, C.P. 6128, succursale Centre-Ville, Montreal, H3C 3J7, Canada. nancy.sheehan@umontreal.ca
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Sheehan
authors.forename: Rolf P G
authors.initials: RP
authors.lastname: van Heeswijk
authors.forename: Brian C
authors.initials: BC
authors.lastname: Foster
authors.forename: Humayoun
authors.initials: H
authors.lastname: Akhtar
authors.forename: Neera
authors.initials: N
authors.lastname: Singhal
authors.forename: Isabelle
authors.initials: I
authors.lastname: Seguin
authors.forename: Lina
authors.initials: L
authors.lastname: DelBalso
authors.forename: Marc
authors.initials: M
authors.lastname: Bourbeau
authors.forename: Bobby M
authors.initials: BM
authors.lastname: Chauhan
authors.forename: Mohammed-Rachid
authors.initials: MR
authors.lastname: Boulassel
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
authors.forename: Richard G
authors.initials: RG
authors.lastname: Lalonde
authors.forename: Donald William
authors.initials: DW
authors.lastname: Cameron
mesh_terms: D000328:Adult; D019540:Area Under Curve; D019587:Dietary Supplements; D004355:Drug Stability; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D019562:Viral Load; D019207:beta Carotene / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D017320:HIV Protease Inhibitors; C517960:M8-nelfinavir; D019207:beta Carotene; D019888:Nelfinavir