Oral Administration of Codeine in the Presence of Ethanol: A Pharmacokinetic Study in Man

Abstract

Three healthy male volunteers were given a codeine (1 mg/kg) solution in the absence and presence of ethanol in a cross-over designed study. The blood ethanol concentration was kept at approximately 16 mM for 8 hrs. Blood samples were taken at several occasions during the first day after the codeine administration. Urine was sampled during three days. There were no significant differences in the area under serum concentration versus time curve in the absence and presence of ethanol with respect to free codeine, total codeine and total morphine. The fraction of codeine glucuronized in serum (approximately 94%) the maximum serum concentration of free (0.34 .mu.M) and total codeine (6.3 .mu.M), the time to reach the maximum serum concentration values (approximately 65 min.) were also similar in the absence and presence of ethanol. The accumulated percentage of the codeine dose given which was found as codeine and morphine and their conjugates in the urine ranged from 50 to 91 percent in the different subjects. The accumulated percentage of the administered codeine dose found as free morphine in the urine, was significantly lower in the ethanol exposed individuals (0.18 .+-. 0.03%) compared to the controls (0.39 .+-. 0.09%). The percentage of the codeine dose found in the urine in the control situation as free codeine (5.2 .+-. 2.2%) was not statistically different from the amount found in the urine after ethanol treatment (4.3 .+-. 2.0%). The percentage glucuronized morphine (95.3 .+-. 0.4%) and codeine (93.1 .+-. 2.2%) in the urine in the absence of ethanol was similar to glucuronized morphine (95.3 .+-. 2%) and codeine (93.1 .+-. 3%) after ethanol exposure. The results suggest that there is probably no significant biological interaction of ethanol with codeine pharmacokinetics in vivo in humans.