Effect of quercetin on the plasma and intracellular concentrations of saquinavir in healthy adults

Study Objectives. To determine if quercetin, a bioflavonoid that inhibits p-glycoprotein, alters plasma saquinavir concentrations, and to explore the potential influence on intracellular concentrations. Design. Prospective pharmacokinetic analysis. Setting. University-affiliated general clinical research center. Subjects. Ten healthy adults (four women, six men) with a mean ± SD age of 30.7 ± 9.4 years. Intervention. 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. Measurements and Main 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 (AUC_0-8), 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 AUC_0-8 = 0.51 [95% CI 0.14-1.95], six patients). Conclusion. 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.