1. Serum and urinary levels of S-6436 500mg P.O. were determined in two volunteers with normal renal function. In one case, S-6436 was orally administrated at 30 minutes after light meal and in another case, at 60 minutes after usual meal. The peak serum level of Cephalexin (CEX) was 6.4μg/ml at 4 hours in the former and 7μ/ml at 6 hours in the latter after oral administration. The time length, in which more than 3μg/ml serum level was kept, was 6 hours in the former and 4 hours in the latter. The peak urinary levels were 1, 350 in the former and 2, 100μg/ml in the latter in 4-6 hours after administration. The recovery rates from urine for 12 hours after the administration were 93.8% and 93.3%, respectively.
2. 72 adult U.T.I. patients were treated with daily dosage of 250mg or 500mg b.i.d. of S-6436 for 7 days. The criteria recommended by U.T.I. Drug Evaluation Committee in Japan were applied for clinical evaluation of S-6436. Eight patients were eliminated from the subject for efficacy evaluation, by the reason that their pathogen could not found before the treatment, and remaining 64 patients were evaluated for the drug efficacy. Dosage regimens administrated and the respective numbers of patients were as follows: S-6436 500mg b.i.d. after meals, 36; and S-6436 250mg b.i.d. after meals, 28.
Clinical responses of 36 patients with S-6436 500mg b.i.d. after meals for 7 days were as follows:
a) Of 18 with acute simple cystitis, 15 were rated excellent and 3, good.
b) Of 9 with chronic complicated cystitis, 3 were rated excellent, 1, good and 5, poor.
c) Of 7 with chronic complicated pyelonephritis, 1 was rated excellent, 3, good and 3, poor.
d) Other 2 cases were rated excellent.
Clinical responses of 28 patients with S-6436 250mg b.i. d. after meals for 7 days were as follows:
a) Of 26 with acute simple cystitis, 24 were rated excellent and 2, good.
b) One chronic complicated cystitis was rated good.
c) One acute simple pyelonephritis was rated excellent In acute cystitis, conclusively, S-6436 250mg b.i.d. was equal to 500mg b.i.d. in the effectiveness.
3. S-6436 was well tolerated in oral administration. Three cases of adverse reactions, mild nausea, epigastric discomfort and glossitis, respectively, were obserbed in 500mg b.i.d. group. The treatment was discontinued in only one patients of glossitis. A transient and slight rise in S-GOT, S-GPT value was observed in two patients treated with 500mg b.i.d.
4. The results suggest that S-6436 and CEX are equally effective and safe in the treatment of urinary tract infections. It is considered that S-6436 500mg b.i.d. after meals is mare acceptable and more convenient for the patients than CEX, 250mg q.i.d.
