泌尿器科領域におけるPipemidic acidの基礎と臨床

抄録

Fundamental and clinical studies were carried out on a new synthetic antibacterial drug, pipemidic acid (PPA). The results obtained were as follows.
1. In the sensitivity distribution of various organisms isolated from urinary tract infections, the peak MIC values were 1. 56 μg/ml in E. coli, 3. 13-25 μg/ml in Klebsiella, 3. 13 μg/ml in Proteus, 25 μg/ml in Pseudomonas and 25 μg/ml in Staphylococcus. PPA was 2 to 4 times more potent than nalidixic acid (NA) and 8 to 16 times more potent than piromidic acid (PA) against E. coli, Klebsiella and Proteus. The MIC distribution of PPA was similar to that of NA and aminodeoxykanamycin in Serratia strains which were relatively sensitive to gentamicin.
2. When PPA was given to 2 healthy human male adults at a single oral dose of 1 g, the average peak plasma level was 5. 5 μg/ml 2 hours after dosing and the average peak urine level was 3, 250μg/ml in 1-2 hour urine. The urinary recovery for 12 hours was 55.6% on th average.
When 250 mg of PPA was orally given to 5 healthy male adults, the peak concentration in plasma was 1. 9 μg/ml on the average 1 hour after dosing. The highest average concentration of 620 μg/ml was observed in 0-2 hour urine and the average urinary recovery was 80%.
In a patient with renal insufficiency receiving PPA at a single oral dose of 500 mg, the plasma level attained a peak of 43. 5 μg/ml 1 hour after dosing and was 27. 5 μg/ml even 8 hours later. The urinary recovery for 8 hours was 2.6%.
3. PPA was used for 157 cases of urinary tract infections with the results of 92 excellent, 51 good, 13 ineffective and 1 unknown cases. The rate of effectiveness was 91.7%.
In 92 cases of simple urinary tract infections, 62 cases were excellent, 26 cases good and 4 cases ineffective, the rate of effectiveness being 95. 7%. In 65 cases of complicated urinary tract infections, 30 cases were excellent, 25 cases good and 9 cases ineffective, the rate of effectiveness being 85.9%. When classified according to causative organisms, the rate of effectiveness ranged between 85.7 and 100% in the infections due to E. coli, Klebsiella, Proteus and Pseudomonas. PPA was clinically effective against organisms resistant to NA, ampicillin and cephalexin as expected from its in vitro result that there is no cross-resistance between PPA and NA or antibiotics.
4. Nausea was observed in 3 (1.9%) of 157 cases treated with PPA. Medication was discontinued in 1 case due to the side effect, but the other 2 cases ceased complaining in spite of continued medication of PPA. No abnormalities were observed with respect to blood analysis, liver and kidney function tests in 10 cases examined before and after medication.