ANALGESIC EFFECT AND PLASMA-CONCENTRATIONS OF CODEINE AND MORPHINE AFTER 2 DOSE LEVELS OF CODEINE FOLLOWING ORAL-SURGERY

A double blind randomised cross over investigation was carried out in 25 male patients undergoing two oral surgical extractions, one for eac h lower wisdom tooth. The two extractions were performed about 6 weeks apart and were carried out under local anaesthesia. One hour after ea ch extraction the patients randomly received 90 or 45 mg codeine. Duri ng the following 5 h the patients rated the intensity of their pain on a visual analogue scale. Blood was simultaneously sampled and assayed for codeine and its metabolite morphine. Mean pain intensity differen ce was just significantly higher after 90 mg codeine compared to 45 mg . The mean plasma concentrations of codeine and morphine were signific antly higher after the 90 mg dose. However, for the two dose levels of codeine there was no obvious relationship between the difference in a nalgesic effect and the difference in the plasma concentration of code ine or morphine. The plasma concentrations of morphine were 2-3 % of t hose of codeine and the levels were relatively low. Local formation of morphine from codeine within the human brain should therefore be inve stigated. Four patients were unable to demethylate codeine to a detect able plasma concentration of morphine after 90 mg codeine. In those pa tients the analgesic effect during the first hours was better after 90 mg codeine than after 45 mg. This suggests some analgesic effect of c odeine itself.