[Phase I clinical studies of S6472 (sustained release preparations of cefaclor)]

Current (regular) preparation of cefaclor (CCL) require the 3-time-a-day administration. S6472 (sustained release preparation) which can be used with the twice-a-day administration in the morning and the evening is capsule and granule preparations consisting of 40% of nonenteric and 60% of enteric coated granules of CCL. Phase I clinical studies of S6472 were conducted in 12 nonfasted healthy adult male volunteers with cross over method using a single dose of 375 mg in capsule and granule forms of S6472, and 250 mg in capsule form of regular CCL as a control drug. The volunteers received the 3 preparations at 1-week interval. The summary of the results from the above studies is as follows: Grouping of the volunteers. The 12 volunteers were divided into 3 groups (each group consists of 4 volunteers) and there were no significant differences between each group regarding background factors of the volunteers. Tolerance. None of the volunteers who received the 3 preparations at 1-week interval complained of subjective abnormalities. No abnormalities which are considered to be due to S6472 and regular CCL were found in the clinical laboratory tests carried out before the administration and 1 week after the completion of the studies. Plasma level. There were no significant differences between capsule and granule forms of S6472 regarding Cmax and AUC, and it was confirmed that bioavailability of both preparations was the same. It was also confirmed that plasma levels of the 2 preparations of S6472 were maintained for longer period of time than those of regular CCL. Urinary excretion. Mean urine levels of the 2 preparations of S6472 every 2 hours after the administration were confirmed to be maintained for longer period of time than those of regular CCL. There were no significant differences between the 2 preparations of S6472 regarding urinary recovery rate. However, the significant differences between the 2 preparations of S6472 and regular CCL were observed. Urinary recovery rate of the 2 preparations of S6472 was 87 approximately 88% of that of regular CCL.