Abstract
Antibacterial activity, absorption, excretion and clinical effects of PC-904 were studied, and the following results were obtained.
1) Antibacterial activities
MIC of PC-904 against E. coli was more susceptible by 1 to 2 stages than ABPC and CBPC, and against Klebsiella pneumoniae, it was more susceptible by 2 to 5 stages than CBPC. It was noteworthy that PC-904 showed far strong antibacterial activity against Pseudomonas aeruginosa compared with conventional penicillins while it was 1 to 2 stages less than gentamicin.
2) Absorption and excretion
(1) Serum level When 250mg and 500mg of PC-904 were intramuscularly administered to healthy volunteers, serum peak levels were 8.9-10.1μg/ml and 20.3-22.1μg/ml respectively at 60 minutes after administration. PC-904 showed similar decrease pattern of serum levels at both dosage and when 500mg of PC-904 were intramuscularly administered, its serum level was 1.8-2.5μg/ml at 6 hours after. Dose response relationship was apparently observed.
(2) Urinary excretion Average excretion rates of PC-904 in urine after intramuscular injections of 250mg and 500mg within 6 hours were 24.9% and 23. 3%, respectively. The low urinary excretion rate of drug was suggested.
3) Distribution
When 20mg/kg of PC-904 was intramuscularly administered to rats, the concentration of PC-904 was the highest in the liver, then the kidneys, serum and lungs in this order. The peak distribution of PC-904 to experimental pouch transudation was as low as 0.54μg/ml after 1 hour of intramuscular injection. We think that low peak level was caused by its high protein binding ratio of more than 90%.
4) Clinical effects
PC-904 was adminstered to 6 cases of respiratory tract infections, 1 case of cervical lymphadenitis, 2 cases of biliary tract infections, 12 cases of urinary tract infections and 3 cases of septicemia, totally 25 cases, at the dosage of 1.0-9.0g/day for 1-13 days. Effectiveness were shown good in 14 (efficacy ratio: 60.9%), fair in 3, poor in 6 and unknown in 2 cases.
