title: Dose-hair concentration relationship and pigmentation effects in patients on low-dose clozapine.
abstract: Several hair components have been suggested as possible molecular sites for drug binding and interaction. Of these, keratin and melanin have been investigated in some detail in order to assess the mechanisms by which the binding occurs. Substances that are positively charged at physiological pH may interact by electrostatic forces between their cationic groups and the anionic carboxylic groups on the surface of the melanin polymer. Studies in human subjects with grey hair have shown that various drugs are detectable in both the coloured (melanin rich) and white (melanin free) hair shafts of these individuals. Again this supports the proposition that keratin and hair proteins play an important role in the binding of drugs in hair. However, drugs are often found in significantly higher concentrations in pigmented hair strands than in senile white hair strands. Another interesting question is if the concentration measured in hair reflects the dose taken. Previous reports have both verified and rejected this hypothesis, but most agree that many factors have impact on the incorporation rate, melanin being one. In this study we obtained blood and hair samples from 12 grey haired patients treated with low-dose clozapine as an adjunct medication in their treatment against Parkinson disease. Each patient's hair was divided into a pigmented and a non-pigmented portion and those were analyzed separately. Clozapine and desmethylclozapine were analyzed with LC-MS-MS after extraction of the analytes from hair and plasma. Paired results from the analysis of pigmented and white hair confirmed the preference for binding to pigmented hair for both clozapine and its metabolite. A majority of the incorporated clozapine was found in the pigmented hair but, as drugs could be detected in white hair, binding to hair protein or association with other hair matrix account for a significant part of drug accumulation in hair. High correlations between dose and the measured concentration of analyte were found for both clozapine (r = 0.91) and desmethylclozapine (r = 0.88).
authors: Department of Forensic Genetics and Forensic Chemistry, National Board of Forensic Medicine, Linkoping, Sweden.
authors: R
authors: R
authors: Kronstrand
authors: M
authors: M
authors: Roman
authors: M
authors: M
authors: Hedman
authors: J
authors: J
authors: Ahlner
authors: N
authors: N
authors: Dizdar