PT - JOURNAL ARTICLE AU - J Shah AU - W D Mason TI - Pharmacokinetics of codeine after parenteral and oral dosing in the rat. DP - 1990 Sep 01 TA - Drug Metabolism and Disposition PG - 670--673 VI - 18 IP - 5 4099 - http://dmd.aspetjournals.org/content/18/5/670.short 4100 - http://dmd.aspetjournals.org/content/18/5/670.full SO - Drug Metab Dispos1990 Sep 01; 18 AB - The pharmacokinetics of codeine was examined in six male Sprague-Dawley rats following iv bolus (3 mg/kg) and oral (5 mg/kg) codeine in a randomized crossover design. Whole blood concentrations of codeine and its O-demethylated metabolite, morphine, were determined by HPLC with electrochemical detection. Following iv codeine administration, the distribution and elimination are best described by an open two-compartment model. The weight normalized volume of distribution of (Vdarea) and total body clearance (CL) were 5.1 +/- 1.7 liters/kg and 6.2 +/- 1.5 liters/kg/hr, respectively. Mean residence time of codeine averaged 34.1 +/- 6.9 minutes. The ratio of AUCmorphine/AUCcodeine was 0.05 +/- 0.02. The absolute bioavailability of codeine calculated was 8.3 +/- 3.2%, indicating extensive first pass metabolism of codeine. An equivalent amount of codeine and morphine were present in the rat following oral codeine. Thus, the amount of morphine formed following codeine administration depends on the route of codeine administration.