The effect of β-carotene supplementation on the pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1-infected patients

Nancy L. Sheehan, Rolf P G Van Heeswijk, Brian C. Foster, Humayoun Akhtar, Neera Singhal, Isabelle Seguin, Lina DelBalso, Marc Bourbeau, Bobby M. Chauhan, Mohammed Rachid Boulassel, David M. Burger, Richard G. Lalonde, Donald William Cameron

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)688-702
Number of pages15
JournalMolecules
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 2012

Fingerprint

Nelfinavir
carotene
human immunodeficiency virus
Pharmacokinetics
metabolites
Carotenoids
Metabolites
HIV-1
Cytochrome P-450 Enzyme System
Area Under Curve
transporter
CD4-CD8 Ratio
cytochromes
supplements
serums
enzymes
confidence
Assays
Confidence Intervals
intervals

Keywords

  • β-carotene
  • HIV
  • Interaction
  • Nelfinavir
  • Pharmacokinetics

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Sheehan, N. L., Van Heeswijk, R. P. G., Foster, B. C., Akhtar, H., Singhal, N., Seguin, I., ... Cameron, D. W. (2012). The effect of β-carotene supplementation on the pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1-infected patients. Molecules, 17(1), 688-702. https://doi.org/10.3390/molecules17010688

The effect of β-carotene supplementation on the pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1-infected patients. / Sheehan, Nancy L.; Van Heeswijk, Rolf P G; 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.

In: Molecules, Vol. 17, No. 1, 01.2012, p. 688-702.

Research output: Contribution to journalArticle

Sheehan, NL, Van Heeswijk, RPG, Foster, BC, Akhtar, H, Singhal, N, Seguin, I, DelBalso, L, Bourbeau, M, Chauhan, BM, Boulassel, MR, Burger, DM, Lalonde, RG & Cameron, DW 2012, 'The effect of β-carotene supplementation on the pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1-infected patients', Molecules, vol. 17, no. 1, pp. 688-702. https://doi.org/10.3390/molecules17010688
Sheehan, Nancy L. ; Van Heeswijk, Rolf P G ; 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. / The effect of β-carotene supplementation on the pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1-infected patients. In: Molecules. 2012 ; Vol. 17, No. 1. pp. 688-702.
@article{6bfd69b7ec234c1ea39fcb29760461e1,
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 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.",
keywords = "β-carotene, HIV, Interaction, Nelfinavir, Pharmacokinetics",
author = "Sheehan, {Nancy L.} and {Van Heeswijk}, {Rolf P G} and Foster, {Brian C.} and Humayoun Akhtar and Neera Singhal and Isabelle Seguin and Lina DelBalso and Marc Bourbeau and Chauhan, {Bobby M.} and Boulassel, {Mohammed Rachid} and Burger, {David M.} and Lalonde, {Richard G.} and Cameron, {Donald William}",
year = "2012",
month = "1",
doi = "10.3390/molecules17010688",
language = "English",
volume = "17",
pages = "688--702",
journal = "Molecules",
issn = "1420-3049",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "1",

}

TY - JOUR

T1 - The effect of β-carotene supplementation on the pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1-infected patients

AU - Sheehan, Nancy L.

AU - Van Heeswijk, Rolf P G

AU - Foster, Brian C.

AU - Akhtar, Humayoun

AU - Singhal, Neera

AU - Seguin, Isabelle

AU - DelBalso, Lina

AU - Bourbeau, Marc

AU - Chauhan, Bobby M.

AU - Boulassel, Mohammed Rachid

AU - Burger, David M.

AU - Lalonde, Richard G.

AU - Cameron, Donald William

PY - 2012/1

Y1 - 2012/1

N2 - 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 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.

AB - 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 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.

KW - β-carotene

KW - HIV

KW - Interaction

KW - Nelfinavir

KW - Pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=84856149488&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856149488&partnerID=8YFLogxK

U2 - 10.3390/molecules17010688

DO - 10.3390/molecules17010688

M3 - Article

VL - 17

SP - 688

EP - 702

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 1

ER -