Inhibition of alfentanil metabolism by erythromycin

To investigate a possible connection between erythromycin administration and reduced elimination of alfentanil, a controlled crossover study of alfentanil pharmacokinetics was undertaken. Six subjects were monitored for alfentanil plasma levels for 8 hours after alfentanil was administered. These measurements were obtained after a 0-, 1-, and 7-day course of erythromycin. Elimination half-life increased significantly (p less than 0.01) after 7 days from the control value of 84.0 +/- 8.2 minutes to 131.4 +/- 43.5 minutes. Clearance was decreased significantly (p less than 0.05) from 3.9 +/- 0.8 ml/kg/min to 2.9 +/- 1.2 ml/kg/min after 7 days. Values after 1 day were intermediate. Distribution volume did not change significantly. Subjects differed sharply in their sensitivity to erythromycin. Because of the interaction between erythromycin and alfentanil, we recommend that patients who are receiving erythromycin should be given alfentanil in reduced amounts or should avoid the drug completely.