Abstract
On PC-904, fundamental experiment and clinical evaluation were performed.
1. The degree of binding of PC-904 to human serum protein was more than that of other penicillins: 99% of PC-904, 96% of penicillin G, 48% of sulbenicillin, 38% of ampicillin and 28% of carbellicillin.
2. PC-904 was incubated individually with each of the following aminoglycoside antibiotics: gentamicin, dibekacin, tobramycin, KW-1062, lividomycin and amikacin. The residual activity of each aminoglycoside in this mixture was measured by bioassay. Amikacin and lividomycin remained almost active, but other aminoglycosides were inactivated by the mixture of PC-904.
3. Serum levels of PC-904 were measured in 2 realthy adults and 2 patients with moderately impaired renal function (Creatinine clearance 55.4 and 41. 5 ml/min) after 500 mg of PC-904 were administered by drip infusion for 2 hours. Serum half-lives were 0.52 and 0.73 hours in the healthy adults. On the other hand, these times were 0.42 and 1.15 hours in the patients with impaired renal function. Urinary recoveries were 20 and 15.9% in the healthy adults, but in the patients with impaired renal funtion were decreased to 10.6 and 11.6%.
4. No active metabolite was demonstrated in urine from healthy adult after the dministration of PC-904.
5. The clinical evaluation of PC-904 was performed in 10 patients: 4 patients with lower respiratory tract infections, 3 patients with lower urinary tract infections, each one with cholecystitis, bacterial endocarditis and meningitis. The treatment with PC-904 enabled a complete clinical success to be achieved in 5 cases, a partial success being obtained in a further 2 cases. For the side effect of PC-904, there were rash and fever in a patient, and eosinophilia in another patient.
