THE EFFECT OF CIMETIDINE ON THE PHARMACOKINETICS OF SINGLE ORAL DOSESOF ALFUZOSIN

Alfuzosin is a new alpha(1)-adrenoceptor antagonist particularly effec tive in the symptomatic treatment of benign prostatic hypertrophy (BPH ). The elimination of alfuzosin being almost entirely metabolic, the p otential pharmacokinetic interaction with cimetidine (H-2-receptor ant agonist) was investigated in 10 healthy young subjects. Pharmacokineti cs of alfuzosin were appraised as a 5 mg oral dose before, after one d ay and after 20 days of cimetidine (1 g/d) administration. An inhibiti on of the hepatic mixed function oxidase system by cimetidine was esta blished by the oral antipyrine clearance test. Under these conditions, alfuzosin pharmacokinetics were only marginally affected by concomita nt cimetidine administration. Surprisingly, a significantly shorter el imination half-life was found after 20 days on cimetidine (from 5.1 +/ - 0.4 h to 4.4 +/- 0.5 h). This fact must be attributed to the large i nter-individual variation in pharmacokinetic parameters reported for a lfuzosin. C-max and AUC increased up to 20% after cimetidine but witho ut statistical significance. No side-effects on the association cimeti dine-alfuzosin were reported. In conclusion, there is a lack of pharma cokinetic interaction on cimetidine-alfuzosin co-administration.