INTERACTION BETWEEN ERYTHROMYCIN AND NITRAZEPAM IN HEALTHY-VOLUNTEERS

Interaction between erythromycin, a strong inhibitor of CYP3A4, and ni trazepam, a long-acting benzodiazepine, was investigated in a double-b lind and randomized cross-over study of two phases. Ten healthy volunt eers received erythromycin (500 mgX3) orally or placebo for 6 days. On the fourth day they were given a challenge dose of 5 mg nitrazepam. P lasma samples were collected and psychomotor effects were measured dur ing 42 hr after intake of nitrazepam. There was a statistically signif icant pharmacokinetic interaction between erythromycin and nitrazepam. Erythromycin increased the area under the nitrazepam concentration-ti me curve by 25% (P<0.05) and the peak concentration by 30% (P<0.05). T he concentration peak time of nitrazepam was shortened by over 50% (P< 0.05). The elimination half-lives did not change. Accordingly, as far as the metabolism of nitrazepam is concerned, erythromycin does not ca use any major changes in the metabolism of nitrazepam. In psychomotor performance only minor differences were seen. It is concluded that the interaction between erythromycin and nitrazepam is of little clinical significance.