Pharmacokinetic Characteristics of a Vasodilatory and Antiplatelet Agent, Limaprost Alfadex, in the Healthy Korean Volunteers

Abstract

Limaprost, a prostaglandin E1 analogue, with a strong vasodilatory and antiplatelet activity has been used to release from the symptoms of thromboangiitis obliterans (TAO), which is more prevalent in Korea and Japan, and lumbar spinal canal stenosis (LSCS). In spite of many uses of limaprost, the pharmacokinetics (PK) of it has not been studied in the Korean population. Therefore, a preliminary PK study was designed at a clinical oral dosage of 30-mu g limaprost in 5 healthy Korean volunteers. Blood samples were obtained at 14 consecutive time points for 12 hours after dosing and analyzed by liquid chromatography-tandem mass spectrometry with electrospray ionization (LC-ESI/MS/MS) at a very low detection limit of 0.5 pg/mL of limaprost in human plasma with considerably short run time (18 minutes). Pharmacokinetic characteristics resulted in "time for maximal concentrations (T(max) 0.5 hour)," "elimination half-life (T(1/2) 1.64 hours)," "maximal concentration (C(max) 13.37 pg/mL)," "area under the curve (AUC(12) (hours) 18.60 pg.h/mL)," "AUC extrapolated to infinity (AUC(infinity) 22.98 pg.h/mL)," "extrapolation (AUC(infinity -) (12 hours)/AUC(infinity) 0.15%)," "elimination rate constant (k(e) 0.68 h(-1))," "systemic clearance (CL 1.77 L/h)," and "mean residence time (MRT 1.74 hours)." These results showed that orally administered 30-mu g limaprost was rapidly and highly absorbed, and it was considerably eliminated fast from the blood stream in the healthy Korean volunteers.