Effect of quercetin on the plasma and intracellular concentrations of saquinavir in healthy adults.
OBJECTIVE
To determine if quercetin, a bioflavonoid that inhibits p-glycoprotein, alters plasma saquinavir concentrations, and to explore the potential influence on intracellular concentrations.


METHODS
Prospective pharmacokinetic analysis.


METHODS
University-affiliated general clinical research center.


METHODS
Ten healthy adults (four women, six men) with a mean +/- SD age of 30.7 +/- 9.4 years.


METHODS
All subjects received saquinavir 1200 mg 3 times/day with food on days 1-11 and quercetin 500 mg 3 times/day with food on days 4-11.


RESULTS
On days 4 and 11, nine blood samples and four peripheral blood mononuclear cell samples were drawn during a steady-state dosing interval. Pharmacokinetic parameters were calculated by using standard noncompartmental techniques. Plasma saquinavir concentrations were similar regardless of quercetin administration. Geometric mean ratios for the area under the concentration-time curve during an 8-hour dosing interval (AUC0-8), maximum concentration in the dosing interval, and minimum concentration in the dosing interval were 0.99 (95% confidence interval [CI] 0.65-1.50), 0.99 (95% CI 0.64-1.54), and 1.06 (95% CI 0.68-1.67), respectively. Intracellular saquinavir concentrations displayed substantial intra- and intersubject variability, which limited the ability to determine the influence of quercetin coadministration (geometric mean ratio for AUC0-8 = 0.51 [95% CI 0.14-1.95], six patients).


CONCLUSIONS
Quercetin coadministration did not influence plasma saquinavir concentrations. Because of substantial inter- and intrasubject variability, more study is necessary to determine if saquinavir intracellular concentrations are altered by coadministration of quercetin.
DiCenzo
Robert
R
School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, 14642, USA. robert_dicenzo@urmc.rochester.edu
Frerichs
Valerie
V
Larppanichpoonphol
Panupong
P
Predko
Lisa
L
Chen
Amy
A
Reichman
Richard
R
Morris
Marilyn
M
D000328:Adult; D005260:Female; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D011794:Quercetin / Q000494:pharmacology*; D019258:Saquinavir / Q000097:blood / Q000493:pharmacokinetics*
D017320:HIV Protease Inhibitors; D011794:Quercetin; D019258:Saquinavir