The effect of rifampin administration on the disposition of fexofenadine

Objective: Our objective was to assess the effect of rifampin (INN, rifampi cin) on the pharmacokinetics of fexofenadine and to assess the influence of advanced age and sex. Methods: Twelve young volunteers (6 men and 6 women; age range, 22 to 35 ye ars) and twelve elderly volunteers (6 men and 6 women; age range, 65 to 76 years) received a 60-mg oral dose of fexofenadine before and after treatmen t with 600 mg of oral rifampin for 6 days. Blood and urine were collected f or 48 hours and assayed for fexofenadine, azacyclonol, and rifampin by HPLC with either fluorescence or mass spectrometry detection. Results: All of the groups had a significant increase (P < .05) in the oral clearance of fexofenadine after rifampin treatment: young men, 2955 <plus/ minus> 1516 versus 5524 +/- 3410 ml/min; young women, 2632 +/- 996 versus 7 091 +/- 5,379 ml/min; elderly men, 1760 +/- 850 versus 4608 +/- 1159 ml/min ; and elderly women, 2210 +/- 554 versus 4845 +/- 1600 ml/min. The peak ser um concentration of fexofenadine was also significantly reduced (P < .05) b y rifampin treatment: young men, 77 <plus/minus> 31 versus 52 +/- 17 ng/mL; young women, 72 +/- 19 versus 36 +/- 14 ng/mL; elderly men, 106 +/- 42 ver sus 52 +/- 14 ng/mL; elderly women, 76 +/- 23 versus 46 +/- 19 ng/mL. Half- life (150 to 230 minutes), time to maximum concentration (130 to 205 minute s), renal clearance (95 to 153 ml/min), and fraction unbound (2.9% to 3.7%) of fexofenadine showed no significant difference between control and treat ment. The amount of azacyclonol, a CYP3A4 mediated metabolite of fexofenadi ne, eliminated renally increased on average 2-fold after rifampin dosing; h owever, this pathway accounted for less than 0.5% of the dose. No effect of age or sex on fexofenadine disposition or serum trough rifampin concentrat ion (0.2 mug/mL to 1.8 mug/mL) was observed before or after rifampin treatm ent. Conclusion: This study showed that rifampin effectively increased fexofenad ine oral clearance and that this effect was independent of age and sex. We conclude that the cause of the increased oral clearance of fexofenadine is a reduced bioavailability caused by induction of intestinal P-glycoprotein.