Mechanisms of phencyclidine incorporation into hair

The incorporation of drugs into hair is an area of increasing scientific interest. The purpose of this project was to investigate the mechanisms of incorporation and retention of xenobiotics in the hair of laboratory rodents using phencyclidine (PCP) as a model compound. The incorporation of PCP into the pigmented and nonpigmented hair of Long-Evans (LE) rats increased as the dose of PCP was increased. There was a 30-fold greater incorporation into pigmented hair compared to nonpigmented hair from the same animal. The hair concentration (ng/mg) of PCP was not changed in spite of different amounts of hair collected from distinct dosing intervals in the same group of LBNFI rats. A single dose of PCP was detected in terminal segments of collected rat hair. However, it was possible to localize the discrete band of PCP to within only 50% of the hair length. The potential for PCP to be retained within hair via an ionic mechanism was investigated by altering the ionic equilibrium of PCP with buffers of varying pH in an attempt to displace PCP from binding sites within the hair. Increasing the pH of the extraction buffer, increased the amounts of PCP removed from pigmented LE rat hair. The same PCP extraction pattern was not seen for nonpigmented LE hair. Phenobarbital showed no pH-dependent extraction from pigmented LE rat hair. These data were further supported by in vitro incubations with sepia melanin. These results suggested that noncationic drug forms (i.e., phenobarbital) have a lesser capacity for binding with melanin, both in hair and in vitro. Rodent hair with eumelanin as the principle pigment incorporated more PCP than rodent hair with either no melanin or pheomelanin as the principle pigment. The data from this dissertation have demonstrated that PCP is a useful model drug for studying the mechanisms of drug incorporation and retention in hair. Results indicate that PCP is retained within pigmented hair via an ionic interaction with eumelanin. Eumelanin appears to playa larger role than pheomelanin in incorporating PCP into hair.