rimoprostil (Ro 21-6937), an analog of PGE2, was previously evaluated to assess its inhibitory effect in stimulated gastric secretion, and was found to be active when administrated orally. The purpose of this study was to determine the safety, tolerance and pharmacokinetic profile of trimoprostil following single oral administration (250, 500 and 1, 000 μg) and multiple dosing regimen (500 μg 4 times a day for 7 days) in healthy volunteers and also, to determine the pharmacokinetic profile of trimoprostil (500 μg 4 times a day) 30 min after every meal. Plasma concentrations of this compound were determined by enzyme immunoassay and GC-MS methods. Administra tion of trimoprostil in single or multiple dose regimen had no significant effects on vital signs (blood pressure, pulse rate, respiration rate, body temperature), subjective symptoms, ECG, or clinical laboratory test data in this study. Dose-related plasma concentration time curves were obtained following single dose. The rate of absorption was diminished following postprandial administration. Because of the rapid elimination of trimoprostil from blood, there was no accumulation of drug in the blood even in a 7-day multiple dose reginem. These results indicate no significant dose-related intorelance which would prohibit the continuation of clinical trials of this compound.
