title: Distribution of codeine and morphine into rat hair after long-term daily dosing with codeine.
abstract: Hair analysis for drugs of abuse provides a possible long-term measure of drug use not possible with urinalysis. Many drugs and their metabolites have been detected in hair; however, the factors influencing the incorporation of chemicals into hair are poorly understood. An animal model for chemical uptake into hair utilizing controlled drug administration was developed to ascertain if increasing doses of codeine are reflected in the concentrations of codeine and its metabolites found in hair. Male Sprague-Dawley rats were administered codeine at 5, 10, or 20 mg/kg (intraperitoneally; n = 6) daily for 21 days. At various times during and after the dosing protocol, approximately 50 mg of hair was shaved from a different area of the animals' backs and analyzed for codeine and morphine concentrations by ion-trap gas chromatography-mass spectrometry. Peak hair codeine concentrations for the 5-, 10-, and 20-mg/kg groups occurred 20 days after beginning the dosing protocol and were 0.57 +/- 0.13, 0.80 +/- 0.10, and 1.95 +/- 0.35 ng/mg hair, respectively. Morphine peak concentrations occurred at the same time and were 1.08 +/- 0.28, 1.21 +/- 0.09, and 2.10 +/- 0.26 ng/mg hair for the 5-, 10-, and 20-mg/kg groups, respectively. Long-term dosing in the rat resulted in similar or greater hair concentrations of morphine (metabolite) than codeine. The plasma pharmacokinetics of codeine and morphine were also obtained after a single, intraperitoneal codeine administration of 20 mg/kg. An experiment involving washing the rat hair with methanol or phosphate buffer (pH 9.0) did not reduce the concentration of codeine or morphine measured in hair as compared with nonwashed control hair. Data obtained in this study indicate that after controlled administration the incorporation of codeine and its metabolite, morphine, into rat hair occurs in a distinct dose-proportional manner.
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Gygi
authors.forename: D G
authors.initials: DG
authors.lastname: Wilkins
authors.forename: D E
authors.initials: DE
authors.lastname: Rollins
mesh_terms: D000818:Animals; D002021:Buffers; D003061:Codeine / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D006197:Hair / Q000737:chemistry / Q000378:metabolism*; D013287:Illicit Drugs / Q000032:analysis / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D000432:Methanol / Q000737:chemistry; D009020:Morphine / Q000032:analysis / Q000493:pharmacokinetics*; D009294:Narcotics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010710:Phosphates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002021:Buffers; D013287:Illicit Drugs; D009294:Narcotics; D010710:Phosphates; D009020:Morphine; D003061:Codeine; D000432:Methanol