Codeine disposition in smokers and nonsmokers

Abstract

The bioavailability of codeine and extent of its transformation to morphine were studied in 12 smoking and 11 nonsmoking subjects after single doses of 60 mg i.m. codeine and 60 mg codeine sulfate orally, given 1 wk apart. Codeine and morphine plasma concentrations over the 12-h period after drug were determined by radioimmunoassay (RIA). No differences were found between smokers and nonsmokers with respect to maximum plasma concentration (Cmax) of codeine, time to attain this concentration (tmax), codeine plasma half-life (t1/2) or areas under plasma concentration-time curves (AUC) for codeine or morphine. There was a faster, but clinically unimportant, mean apparent plasma clearance in smokers (52.8 .+-. 2.3 ml/min per 70 kg) than in nonsmokers (45.0 .+-. 2.1) after i.m. injection only. Mean oral codeine bioavailability in smokers (54.8 .+-. 4.9%) and in nonsmokers (50.2 .+-. 2.1%) did not differ. Plasma morphine AUC values were higher after oral doses than after i.m. injections, suggesting a 1st-pass O-demethylation of codeine. For 6 of these subjects plasma morphine AUC values were very low after both routes of administration, suggesting less O-demethylation of coedine in these than in the remaining 17 subjects. The observation of higher morphine AUC values after oral codeine, coupled with clinical reports of greater analgesic potency with i.m. codeine, does not support the hypothesis that the analgesic properties of this drug are mediated entirely by biotransformation to morphine.