新合成Penicillin PC-904に関する薬理学的研究

第2報 生体内動態

抄録

Fates of PC-904 (half life, distribution, urinary and fecal excretion, transfer to the fetus, binding to protein and partition coefficient), a new semisynthetic penicillin which is effective against severe infections by gram-negative bacilli, were investigated in the rats using-¹⁴C-PC-904.
When rats were intravenously or intramuscularly injected PC-904 and ¹⁴C-PC-904 in a dose of 50mg/kg, biological half lives were 10.56 and 25.48min. respectively by measuring biological activities, or were 13.34 and 23.10min. respectively using radioisotope. The biological half life of PC-904 in the injected site of muscle was 25.96 (biological activities) or 22.14min.(radioisotope). The organ levels attained to maximum within 15min. after administration, and the duodenum and kidney levels were higher than the serum level. The total amount excreted in 24hr. urine of the rat which was injected PC-904 was approximately 11% of the injected amount. Most of this penicillin was excreted within the first 4hr. after administration. The evaluations between biological and radiological activities were not of significant difference. The maximal intestine level of PC-904 moved to lower intestine with course of time. Biologically active PC-904 in the feces was 2.06% and total amount excreted in feces (radioisotope) was 46. 17%. Only PC-904 existed in the urine, and most of a metabolite of PC-904 was existed in the feces.
Therefore, PC-904 is rapidly transfered to the organs from blood, and excreted in the urine and bile. PC-904 is transformed by cleavage its lactam ring in the lower intestine, and excreted in the feces.
The cord blood level of PC-904 was approximately 10% of maternal serum level in the pregnant rats.
A binding rate of PC-904 to human plasma was 93.14%, and approximately half of binding PC-904 had again biological activity by dissociation from protein.