Phase I Clinical Studies of 7432‐S, a New Oral Cephalosporin: Safety and Pharmacokinetics

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Abstract
Phase I clinical studies of 7432‐S, a new oral cephalosporin, including a randomized placebo‐controlled trial were conducted with 40 healthy volunteers, in single‐dose studies, 7432‐S was orally administered at doses of 25, 50, 100, and 200 mg. The mean plasma levels peaked at 2.1 to 3.0 hours and reached 1.9, 3.6, 5.6, and 11.6 μg/ml, respectively. Linear correlation was observed between plasma AUC values and doses given. The half‐lives of the plasma levels were 0.88 to 2.26 hours with a mean of 1.53 ± 0.33 hours. The mean urinary recoveries were 67.5 to 75.2% of the dose within 24 hours. 7432‐S was partially metabolized to 7432‐S‐trans which was excreted in urine at 7.2 to 9.2% of the doses. Study of the meal effect showed that AUC values and peak levels were not altered although the time to the peak levels was slightly prolonged, In multiple‐dose studies, 100 mg of 7432‐S twice daily for 2 weeks and 200 mg twice daily for 1 week were administered and there was no abnormal accumulation of 7432‐S in plasma throughout the study. No significant differences were observed in plasma levels and urinary recoveries between single‐ and multiple‐dose regimens. Clinical symptoms, physical tests, laboratory parameters, and fecal levels of vitamins K1 and K2 were in normal ranges. 7432‐S was concluded to be safe and well tolerated.