A phase I study of EST, a newly synthesized specific thiol protease inhibitor developed as a drug for muscular dystrophy, was performed in healthy adult male volunteers to investigate its safety and pharmacokinetics. EST was administered orally in single doses of 100 mg during fasting, or of 100 mg or 200 mg after a meal. The following results were obtained.
The clinical tests and observation of the subjective and objective signs and symptomsfound no change due to EST.
EST was detected as E-64-c (effective form of EST) in serum and urine after oral administration. The absorption of EST was slower when administered after a meal than during fasting. The AUC (area under the serum concentration curve) and urinary excretion rate were greater following administration after a meal, which indicates a tendency to better bioavailability of EST.
As for the comparison of 100 mg and 200 mg administration after a meal, a distinct dosedependency was observed in the serum concentration and urinary excretion.
