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Authors Li JP, Liu Y, Zhang JR, Yu XT, Wang XL, Zhao LB
Received 2 August 2016
Accepted for publication 8 September 2016
Published 15 November 2016 Volume 2016:10 Pages 3699—3706
DOI https://doi.org/10.2147/DDDT.S118723
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 2
Editor who approved publication: Dr Georgios Panos
Background: The intestinal cytochrome P450 3A (CYP 3A) and P-glycoprotein
(P-gp) present a barrier to the oral absorption of saquinavir (SQV).
Resveratrol (RESV) has been indicated to have modulatory effects on P-gp and
CYP 3A. Therefore, this study was to investigate the effects of RESV on P-gp
and CYP 3A activities in vitro and in vivo on oral SQV pharmacokinetics in
rats.
Methods: In vitro, intestinal microsomes were used to evaluate
RESV effect on CYP 3A-mediated metabolism of SQV; MDR1-expressing Madin–Darby
canine kidney (MDCKII-MDR1) cells were employed to assess the impact of RESV on
P-gp-mediated efflux of SQV. In vivo effects were studied using 10 rats
randomly assigned to receive oral SQV (30 mg/kg) with or without RESV (20
mg/kg). Serial blood samples were obtained over the following 24 h.
Concentrations of SQV in samples were ascertained using high-performance liquid
chromatography-tandem mass spectrometry analysis.
Results: RESV (1–100 µM) enhanced residual SQV (% of control)
in a dose-dependent manner after incubation with intestinal microsomes. RESV
(1–100 µM) reduced the accumulation of SQV in MDCKII-MDR1 cells in a
concentration-dependent manner. A double peaking phenomenon was observed in the
plasma SQV profiles in rats. The first peak of plasma SQV concentration was
increased, but the second peak was reduced by coadministration with RESV. The
mean AUC0–∞ of
SQV was slightly decreased, with no statistical significance probably due to
the high individual variation.
Conclusion: RESV can alter the plasma SQV concentration profiles,
shorten the Tmax of SQV. RESV might also cause a slight
decrease tendency in the SQV bioavailability in rats.
Keywords: resveratrol,
saquinavir, P-glycoprotein, CYP 3A, pharmacokinetic