尿中濃度とMICとの関係からみた持続性抗生物質製剤の検討

抄録

S-6436 is a new long-acting preparation of Cephalexin, expected to provide antimicrobial concentration in the urine for a longer period in order to enhance clinical effect.
S-6436 of 1, 000mg/day (×2) was administrated to 20 cases with urinary tract infections for 1.5 to 7 days, and therapeutic efficacies were evaluated in 16 cases (8 acute cases and 8 of 12 chronic cases). As for the side effects, subjective symptom was observed in only one case, but no abnormal cases on laboratory investigations.
Antimicrobial concentrations of 8 hours-urine following 500mg administration of S-6436 and Cephalexin after meal were measured by cross over method. Peak urinary level of S-6436 was 1, 250μg/mlin 6 hours, and of Cephalexin 1, 800μg/ml in 2 hours. S-6436 and Cephalexin in 61.5% and 72.4% were recovered from the urine within 8 hours, respectively. Administration of S-6436 of 500mg provides urinary antimicrobial concentration in excess of 400μg/ml for at least 7 hours.
In all of the 4 clinically ineffective cases, MICs of Cephaiexin against causative organisms were≥ 400μg/ml, but in all cases in which the causative organisms were eliminated, MICs to the causatives were ≤200μg/ml.
In clinically failured cases, the bacteria did not disappear despite of 6-hours persistence of urinary drug concentration in excess of 400μg/ml. Therapeutic efficacy should be discussed not only from the viewpoint of urinary drug antimicrobial concentration and MIC to the bacteria, but also from the view point of the biological reaction of the host.
At any rate, S-6436 can be rated as an excellent and convenient drug for clinical use with minimum side effects. The most impressive is its long acting ability and persistence of high urinary concentration.