1. Diosmin (DSN) has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro and in vivo in rats, which may have potential to cause P-gp-mediated interactions in humans. The purpose of the present study was to investigate the effect of DSN on pharmacokinetics of fexofenadine (FEX) in healthy human volunteers. 2. An open-label, two-period, sequential study was conducted in 12 healthy male volunteers. A single dose of FEX 120 mg was administered to volunteers during control and treatment phases. A single dose of DSN 500 mg was administered to volunteers daily for period of 10 days. The blood and urine samples were collected at predetermined time intervals after FEX dosing and analyzed by LC-MS/MS. 3. Treatment with DSN significantly increased the peak maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of FEX by 49.2% (523.28 versus 780.63 ng/mL) and 64.4% (3459.48 versus 5687.74 ng h/mL), respectively as compared to control phase. On the other hand, apparent oral clearance (CL/F) of FEX was significantly decreased by 41.3% (37.03 versus 21.75 L/h) and there was no significant change was observed in Tmax, T1/2, and CLr (renal clearance) upon treatment with DSN when compared to control. 4. The results suggest that altered pharmacokinetics of FEX might be attributed to DSN-mediated inhibition of P-gp-mediated efflux in humans. Therefore, we conclude that intake of DSN or dietary supplements containing DSN may potentially increase the absorption or bioavailability of FEX, a P-gp substrate in humans.
Keywords: Bioavailability; P-glycoprotein; diosmin; fexofenadine; pharmacokinetics.