The disposition of a histidine decarboxylase inhibitor (S)-alpha-fluoromethylhistidine in rats.
An amino acid analyser method using ninhydrin was developed for (S)-alpha-fluoromethylhistidine (FMH) with a minimum quantitation limit of 0.2 microgram 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.
Sakurai
E
E
Department of Pharmaceutics I, Tohoku College of Pharmacy, Sendai, Japan.
Niwa
H
H
Yamasaki
S
S
Maeyama
K
K
Watanabe
T
T
D000818:Animals; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D007275:Injections, Intravenous; D008297:Male; D008762:Methylhistidines / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D008762:Methylhistidines; C028309:alpha-fluoromethylhistidine; D006640:Histidine Decarboxylase