[Studies on mechanism of drug incorporation into hair]

Drugs and endogenous compounds circulating in the blood are partially incorporated into the growing hair and are retained there for a long time. Therefore, hair analysis has been used as a useful method for detecting and monitoring drugs from days to years after ingestion. Although numerous drugs and metabolites have been detected in hair, many factors are still not cleared on the mechanisms responsible for the incorporation and retention of drugs in hair. In this study, the incorporation mechanisms of drugs from blood into hair were investigated with respect to the contributions of the physicochemical properties of the drugs. The following conclusions were drawn from the results. 1. Drug concentrations in hair were compared to their pharmacokinetic parameters using an animal model, and it was shown that the incorporation of drugs from plasma into hair distinctly depended upon the physicochemical properties of each drug. 2. As an index of facility of incorporation of a drug into hair, Incorporation Rate (ICR) was defined as the ratio of drug concentration in hair to the area under the concentration versus time curve (AUC) in plasma. The effects of structural factors on ICRs were determined using amphetamine analogs, and it was shown that the basicity and lipophilicity affected the drug incorporation into hair. 3. In in vitro experiments, ICRs positively correlated with melanin affinity and lipophilicity. In particular, melanin affinity principally controls the incorporation of basic drugs into hair. 4. In distinguishing legitimate amphetamine--like OTC drug use from illegal amphetamine/methamphetamine use, hair samples were more useful than urine samples due to the easier long term detection of parent drugs or specific metabolites in hair.