A COMPARISON OF PHENOBARBITAL AND CODEINE INCORPORATION INTO PIGMENTED AND NONPIGMENTED RAT HAIR

Drugs and endogenous compounds circulating in the blood may ultimately become incorporated into a growing hair shaft. Hair analysis for drug s of abuse is a growing field in the area of forensic and clinical tox icology. However, the underlying principles that govern drug incorpora tion into hair are not known. In this study, we examined the incorpora tion of a weak acid, phenobarbital, and a weak base, codeine, into Spr ague-Dawley (SD) rat hair. Codeine or phenobarbital was administered t o male SD rats at 40 mg/kg/day for 5 days by intraperitoneal (ip) inje ction. Hair was collected from the back 14 days after beginning the 5- day dosing protocol and analyzed by gas chromatography/mass spectromet ry (GC/MS) for codeine and phenobarbital. The time-courses of phenobar bital and codeine in plasma were also obtained after a single ip injec tion (40 mg/kg). Concentrations of codeine and phenobarbital in SD hai r samples were 0.98 +/- 0.10 and 17.01 +/- 1.40 ng/mg hair, respective ly. The areas under the curve (AUC) of plasma concentration versus tim e for codeine and phenobarbital were 1.58 and 414.50 mu g h/mu L, resp ectively. Notwithstanding the greater phenobarbital concentrations in hair, when plasma concentrations were considered, codeine was apparent ly incorporated to a 15-fold greater extent than phenobarbital. Becaus e hair pigmentation may be important in drug incorporation, the incorp oration of these two drugs was also studied in Long-Evans (LE; produce s both black and white hair on the same animal) rats after 40 mg/kg/da y of ip drug administration for 5 days. Hair was collected at the same time as the previous experiment. Concentrations of codeine in hair we re 44-times greater in pigmented than nonpigmented hair from the same animals. In contrast, hair concentrations of phenobarbital were identi cal in both pigmented and nonpigmented hair. These data suggest that h air pigmentation greatly affects weak base incorporation but not weak acid incorporation into hair. Because hair concentrations of phenobarb ital are not affected by pigmentation, phenobarbital may be an ideal d rug to separate out factors other than pigmentation involved in incorp oration of drugs into hair.