PHARMACOKINETICS OF ALFENTANIL IN PATIENTS TREATED WITH EITHER CIMETIDINE OR RANITIDINE

The pharmacokinetics of alfentanil were studied after single dose intravenous administration of 125 mug/kg to 19 intensive care unit patients who were divided into 3 groups. Group I was given oral antacid, and groups II and III were given, respectively, cimetidine 1200 mg/day IV and ranitidine 300 mg/day IV for 48 hours before administration of alfentanil. Alfentanil plasma concentrations were determined over the 8 hours following drug administration using a radio immunoassay. Pharmacokinetic parameters were calculated using a noncompartmental analysis. In group II, alfentanil plasma concentrations were significantly higher than in the other groups. In addition, significant changes involving the elimination half-life (142.3 +/- 35 vs 81.14 +/- 11 and 88.1 +/- 33 minutes), total clearance (1.27 +/- 0.5 vs 3.56 +/- 1.17 and 2.74 +/- 1 ml/kg/min) and total volume of distribution related to the pseudo distribution phase (226 +/- 73 vs 336 +/- 76 and 271 +/- 61 ml/kg) were found in group II vs groups I and III. These results suggest that pretreatment with cimetidine alters alfentanil pharmacokinetics after single dose administration. In contrast, ranitidine does not appear to have a significant effect.