DOSE-RELATED DISTRIBUTION OF CODEINE AND ITS METABOLITES INTO RAT HAIR

Drugs and endogenous compounds may be incorporated into the matrix of a growing hair shaft. However, the relationship between incorporation and dose or time course of plasma concentrations is poorly defined. Th e purpose of this study was to compare plasma and hair concentrations of codeine and its metabolites after various doses of codeine. Male Sp rague-Dawley rats had a 1 '' x I '' square shaved from their backs. Co deine was administered by intraperitoneal injection (10, 20, 40, or 60 mg/kg/day) daily for 5 days. Fourteen days after beginning drug admin istration, the original patch was reshaved and newly grown hair was an alyzed for codeine and morphine using GC/MS. The mean concentrations o f codeine in hair for the 10, 20, 40, and 60 mg/kg/day groups were 0.2 9, 0.57, 0.96, and 1.93 ng/mg hair, respectively, and the concentratio ns of morphine were 0.15, 0.28, 0.49, and 0.79 ng/mg hair, respectivel y. The plasma concentration time courses for codeine and morphine were determined after single doses of either 20 or 40 mg/kg. Peak plasma c odeine concentrations for the 20 and 40 mg/kg groups were 1,441 and 2, 452 ng/ml plasma, respectively, and the areas under the plasma concent ration vs. time curve were 699 and 1,581 ng-hr/ml, respectively. Morph ine glucuronide, but not codeine glucuronide, was measured in the hair of rats administered codeine. Codeine was also administered to rats b y constant intravenous infusion 140 mg/kg/day for 5 days). The concent ration of codeine in rat hair after this route of administration was 2 .92 +/- 0.72 ng/mg hair. Codeine and morphine are incorporated into ra t hair in a dose-proportional fashion. Morphine glucuronide can be fou nd in rat hair after codeine administration. The codeine concentration in hair is the same whether the drug is administered by constant intr avenous infusion or daily intraperitoneal injections if the areas unde r the plasma concentration vs. time curve values are considered.