In vivo and in vitro metabolism of [14C]penicillic acid.

In vivo and in vitro studies of the metabolism of [14C]penicillic acid showed a significant uptake of penicillic acid by red blood cells and a significant increase in radioactivity associated with the membrane fraction with time (1-4 hr); however, the majority of the red blood cell activity was intracellular. The 14C-radioactivity concentration in liver fractions (1.5 percent of the administered dose 2 hr following administration) was high in the RNA-DNA and protein fractions. The level of the 14C activity associated with these fractions increased with time (24 hr). Preliminary studies of the in vivo metabolism of [14C]penicillic acid by rats showed that a significant amount of radioactivity was excreted in the urine (82 percent of the administered dose after 7 days), of which strongly acidic urinary metabolites accounted for 23 percent; weakly to moderately acidic, 60 percent; strongly basic, 2 percent; and neutral, 15 percent. Isolation and identification studies of the neutral urinary fraction indicated that the major metabolites are non-ionic macromolecules (Mr < 5000). Biliary metabolites (10 percent of the administered dose 2 hr following administration) were 28 percent strongly acidic and 72 percent weakly to moderately acidic.