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Showing papers by "Steven P. Gygi published in 1996"


Journal Article
TL;DR: It is indicated that pigmented hair possesses a greater capacity to bind and incorporate codeine and its metabolites than does nonpigmented hair and Interpretation of hair concentrations of drugs should involve consideration of hair pigmentation.
Abstract: Xenobiotics circulating in the blood may become incorporated into growing hair. Melanin has affinity for many pharmacologically unrelated drugs and is responsible for the pigmentation in hair. To assess the role of pigmentation in the incorporation of drugs into hair, the distribution of codeine and its metabolites was studied in Sprague-Dawley (SD; white nonpigmented hair), Dark Agouti (DA; brown pigmented hair), and hooded Long-Evans (LE; both black pigmented and white nonpigmented hair) rats. Codeine was administered at a dose of 40 mg/kg/day i.p. for 5 days. Fourteen days after beginning the dosing protocol, hair was collected and analyzed for codeine, and its metabolite, morphine, by positive-ion chemical ionization GC/ion-trap MS. The plasma pharmacokinetics for codeine and morphine were also determined after a single 40 mg/kg injection (equivalent to first dose in 5-day dosing protocol) in all three strains of rats. Hair and plasma codeine and morphine concentrations were also determined after acid hydrolysis to evaluate the presence of glucuronide metabolites. Codeine concentrations in the hair of SD, DA, and pigmented LE hair were 0.98 +/- 0.10, 5.99 +/- 1.24, and 111.93 +/- 18.69 ng/mg hair, respectively; morphine concentrations were 0.34 +/- 0.04, 0.51 +/- 0.11, and 14.46 +/- 1.81 ng/mg hair, respectively; morphine glucuronide concentrations were 0.67 +/- 0.08, 1.04 +/- 0.37, and 13.80 +/- 3.60 ng/mg hair, respectively. Studies examining the in vitro binding of [3H] codeine and [3H]morphine to hair demonstrated both specific and nonspecific binding sites for codeine and morphine. Pigmented hair from LE rats possessed the greatest number of binding sites, white hair from SD rats contained the least, and brown hair from DA rats was intermediate. A time course study of codeine and its metabolites showed pigment-mediated differences in incorporation of codeine and metabolites within a few hours of drug administration. These data indicate that pigmented hair possesses a greater capacity to bind and incorporate codeine and its metabolites than does nonpigmented hair. Interpretation of hair concentrations of drugs should involve consideration of hair pigmentation.

75 citations


Journal ArticleDOI
TL;DR: A sensitive and specific method for the quantitative determination of D,L-methadone (MD) and its metabolites, D, L-2-ethyl-1,5-dimethyl-3, 3-diphenylpyrrolinium (EDDP) and D, l2- methyl-5-methyl-2,3,3-d Diphenyl-1- pyrroline (EMDP), in hair has been developed and has been applied
Abstract: A sensitive and specific method for the quantitative determination of D,t-methadone (MD) and its metabolites, D,L-2-ethyl-l,5dimethyl-3,3-diphenylpyrrolinium (EDDP) and D,t-2-ethyl-5methyl-3,3-diphenyl-l-pyrroline (EMDP), in hair has been developed. Deuterated internal standards of MD, EMDP, and EDDP were added to 20-rag hair samples and digested overnight at room temperature with 1N sodium hydroxide. Calibration standards containing known concentrations of MD, EMDP, and EDDP dried onto human hair were also digested. Digest solutions were extracted by a liquid-liquid extraction procedure and

49 citations


Journal Article
TL;DR: The codeine concentration in hair is the same whether the drug is administered by constant intravenous infusion or daily intraperitoneal injections if the areas under the plasma concentration vs. time curve values are considered.
Abstract: 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. The purpose of this study was to compare plasma and hair concentrations of codeine and its metabolites after various doses of codeine. Male Sprague-Dawley rats had a 1" x 1" square shaved from their backs. Codeine was administered by intraperitoneal injection (10, 20, 40, or 60 mg/kg/day) daily for 5 days. Fourteen days after beginning drug administration, the original patch was reshaved and newly grown hair was analyzed for codeine and morphine using GC/MS. The mean concentrations of codeine in hair for the 10, 20, 40, and 60 mg/kg/day groups were 0.29, 0.57, 0.96, and 1.93 ng/mg hair, respectively, and the concentrations of morphine were 0.15, 0.28, 0.49, and 0.79 ng/mg hair, respectively. The plasma concentration time courses for codeine and morphine were determined after single doses of either 20 or 40 mg/kg. Peak plasma codeine 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 concentration vs. time curve were 699 and 1,581 ng-hr/ml, respectively. Morphine glucuronide, but not codeine glucuronide, was measured in the hair of rats administered codeine. Codeine was also administered to rats by constant intravenous infusion (40 mg/kg/day for 5 days). The concentration of codeine in rat hair after this route of administration was 2.92 +/- 0.72 ng/mg hair. Codeine and morphine are incorporated into rat hair in a dose-proportional fashion. Morphine glucuronide can be found in rat hair after codeine administration. The codeine concentration in hair is the same whether the drug is administered by constant intravenous infusion or daily intraperitoneal injections if the areas under the plasma concentration vs. time curve values are considered.

36 citations