The absorption, distribution and excretion of PC-904 were studied mainly by the intravenous administration in animals such as mice, rats, dogs and rhesus monkeys. The results were as follows:
1. The serum levels of PC-904 following an intravenous injection or drip infusion in animals decreased exponentially. The serum half lives had a tendency to become longer in bigger animal species and at higher doses. The dose response of calculated initial concentrations in sera was obvious. No accumulation was observed after a consecutive administration of daily 100 or 300mg/kg for 2 weeks in rhesus monkeys.
2. PC-904 was distributed in the tissues in the order of liver>kidney>serum>lung>testis, spleen and muscle, when administered intavenously in mice and rats. The distribution and the disappearance were rapid.
3. The urinary recovery rates of PC-904 at a dose of 50 mg/kg were about 11% in rats and less than 10% in dogs. However, the recovery rates in dogs were up to 20% at doses more than 100 mg/kg. Those in rhesus monkey were about 20 to 34% when 100 or 300 mg/kg of PC-904 was administered.
4. The bile level of PC-904 in mice was much higher than that in urine, and the biliary recovery rate in rats was about 65%. It was concluded that the major excretory route of PC-904 in mice and rats was liver-bile duct system.
5. Urinary active metabolites of PC-904 were studied by thin-layer chromatography and bioautography. The only active compound detected in human and animal urine was PC-904 itself. The major metabolite (penicilloic acid of PC-904) and the 4-hydroxy-1, 5-naphthyridine-3-carboxylic acid of the side chain had no antibacterial activity.
6. The stability of PC-904 in biological materials was studied. PC-904 was stable at least for 7 days in fresh human serum and urine at 4°C and-20°C. It was unstable in rat feces at 25°C and in rat liver homogenate at 37°C.
