THE EFFECT OF CODEINE ON GASTROINTESTINAL TRANSIT IN EXTENSIVE AND POOR METABOLIZERS OF DEBRISOQUINE

Methods: Codeine (50 mg) was administered to 12 extensive metabolisers (EM) and 12 poor metabolisers (PM) of debrisoquine. The oro-caecal tr ansit time was estimated by the hydrogen breath test. The urinary excr etion of codeine and metabolites during a 6-h interval was estimated a fter simultaneous analysis of codeine, morphine-3-glucuronide (M3G), m orphine-6-glucuronide (M6G), morphine (M), normorphine (NM), norcodein e, norcodeine glucuronide and codeine-6-glucuronide using HPLC. Result s: The mean transit times after placebo were 1.3 h in the EM and 1.4 h in the PM. The corresponding figures after ingestion of codeine were 2.2 h and 2.1 h. The differences between the groups were statistically and clinically insignificant. The effect of codeine compared with pla cebo was significantly different in both groups. As expected, the meta bolites of the O-demethylation pathway, M, M6G, M3G and NM were signif icantly lower in the PM. Interestingly, the recovery of the dose in th e form of codeine (>1.7 times) and norcodeine (> 2.5 times) was signif icantly higher in the PM, indicating compensatory metabolism via N-dem ethylation. Conclusion: In contrast to the analgesic effect, the prolo ngation of gastrointestinal transit caused by the drug does not depend on the formation of O-demethylated active metabolites M, M6G or NM.