Chronic nifedipine dosing enhances cephalexin bioavailability and intestinal absorption in conscious rats

Cephalexin, a beta-lactam antibiotic, is rapidly absorbed via the di- and t ripeptide intestinal transporters, as for many peptidomimetic drugs. Acute nifedipine has been shown to increase intestinal absorption of several beta -lactams: amoxicillin and cefixime in humans, and cephalexin in the rat. We showed previously that the nervous system was involved in the increasing e ffect of nifedipine on cephalexin intestinal absorption in anesthetized rat s. The aim of the present study was 2-fold: 1) to investigate whether the e ffect of nifedipine is maintained in conscious rats, and 2) to determine wh ether the nifedipine effect will persist during chronic nifedipine administ ration. Acute and chronic oral administration of nifedipine significantly i ncreased oral cephalexin area under the plasma concentration-time curve (34 and 25%, respectively) and maximum concentration in plasma (57 and 51%, re spectively), while the distribution and elimination parameters of intra-art erial cephalexin were not affected by acute or chronic nifedipine administr ation. In conclusion, acute nifedipine effect on intestinal absorption of c ephalexin is independent of anesthesia in rats. Since nifedipine could stil l enhance cephalexin intestinal absorption after a 7-day b.i.d. treatment, it can be envisaged to apply this effect to increase bioavailability of poo rly absorbed peptidomimetic drugs in man.