Phase I study of fk03

Abstract

The safety and pharmacokinetics of FK037 were examined in healthy male volunteers in singleand multiple-dose studies. In the single-dose study, 27 subjects were given intravenously 5-minute infusion of 125, 250 or 500 mg, or 60-minute infusion of 500, 1, 000 or 2, 000 mg of the drug. In the multiple-dose study, 6 subjects were given intravenously 60-minute infusion of 2, 000 mg twice a day for four days and once on day 5 (q 12 h). The results were as follows: 1) In the single-dose study, one subject, during 5-minute infusion of 500 mg in the morning, had shock-like reactions such as discomfort, nausea and hypotension, so the infusion was stopped. The subject recovered from the shock-like reactions in the evening and returned to healthy condition in the next morning. In the multiple-dose study, one subject had a fever due to cold, and was withdrawn from the study before the second dosing on day 1. One subject had a slight headache on day 2. For clinical laboratory tests, slight increases in GPT and LAP in each one subject from the single-and multiple-dose studies were observed. In addition, a slight increase in GPT in one subject from the multiple-dose study were found. These increases were not clinically significant. No other abnormal findings in subjective symptoms, clinical laboratory tests or physical examinations were observed. 2) In the multiple-dose study, the fecal microflora was investigated. No remarkable changes in a total number of aerobes and anaerobes were observed with FK037. 3) In the single-dose study, Cmax and AUC increased in proportion to the dose, suggesting the linear pharmacokinetics of FK037. T112 was 2.30 hours and as much as 95 % of the dose given was excreted in the urine within 24 hours. In the multiple-dose study, Cmax remained constant after day 2, T1/2 was 2.15 hours, and urinary recovery was 89.1 %. The plasma protein binding was 11.4 %. The steady state was attained by day 2 of multiple dosing. From these results, we consider that it is possible to conduct phase II study by taking care of shocklike reactions as observed in cephalosporins. © 1994, Japanese Society of Chemotherapy. All rights reserved.