Ｓ‐Ａｄｅｎｏｓｙｌ‐Ｌ‐Ｍｅｔｈｉｏｎｉｎｅ Ｓｕｌｆａｔｅ Ｔｏｓｙｌａｔｅ（ＦＯ‐１５６１）の臨床第１相試験 Ｉ 点滴静注による単回および連続投与試験

Abstract

Phase I study of S-adenosyl-L-methionine sulfate tosylate (FO-1561) was carried out with 17 healthy male volunteers by single administration and by multiple administrations 2-3 times daily for 2-3 consecutive days. In every case, FO-1561 was dissolved in the solvent, added to 500 ml of Ringer's solution, then administrated by intravenous drip infusion during about 2 hours.Subjective and objective symptoms and signs, physiological examination, hemato logical and biochemical examinations, analysis of blood gasses, urinalysis, and concentration of the drug in blood and urine were investigated during administration and up to 15 hours thereafter.The dose level was increased stepwise from single administration of 100 mg (the lowest dosage) to doses of 300 mg 3 times a day (900 mg/day) for 3 consecutive days (the highest dosage) while confirming safety.As a result, no abnormal symptom was observed except for a single case complaining of a slight and transient headache and feverishness, among the subjective and objective symptoms and signs. In physiological, hematological and blood biochemical examinations, no abnormal value was obtained, which was also the case with gasometricanalysis. In urinalysis, increase of urine volume and subsequent elevations of Na, K, Ca, and Cl in urine were observed in all cases, but these findings are due to the infusion of Ringer's solution and are regarded as a normal phenomenon in this case.Through the pharmacokinetic investigations, it was found that the plasma levels of the drug were elevated in proportion to the dose levels, reaching their maximum right after completion infusion and decreasing with a similar pattern of time course. About 60 % of the dosage was recovered unmodified in the urine within 6 hours after completion of the infusion. No accumulation was observed even in the case of multiple administrations.To conclude, it was confirmed that the drug could be administrated quite safely by intravenous infusion at doses less than 900 mg/day (300 mg × 3 times) for 3 consecutive days without any side effects, and that this treatment would be applicable to the clinical stage.