The Disposition of a Histidine Decarboxylase Inhibitor (S)-α-Fluoromethylhistidine in Rats

Abstract

Abstract An amino acid analyser method using ninhydrin was developed for (S)-α-fluoromethylhistidine (FMH) with a minimum quantitation limit of 0.2 μg mL−1. The assay was used to study the kinetics of FMH in rat. After bolus intravenous administration of FMH hydrochloride hemihydrate (50 mg kg−1), plasma concentration decreased biexponentially with half-lives of 4.4 and 32.7 min. The distribution volumes of the central and peripheral compartments were 127.4 and 166.3 mL kg−1, respectively. The tissue concentration of FMH was highest in the kidney and also decreased biphasically. The FMH concentrations in other tissues were lower, but their tissue/plasma ratios of FMH increased continuously after FMH injection, indicating that FMH partitioned into these tissues and was lost from them very slowly.