METABOLISM OF 2 PGF2-ALPHA ANALOGS IN PRIMATES - 15(S)-15-METHYL-DELTA-4-CIS-PGF1-ALPHA AND 16,16-DIMETHYL-DELTA-4-CIS-PGF1-ALPHA

The metabolism of the prostaglandin F2α analogues, 15-methyl-Δ4-cis-PGF1α and 16,16-dimethyl-Δ4-cis-PGF1α, has been investigated in the cynomolgus monkey and the human female. The two analogues, tritium labelled in the 9β-position, were administered by intramuscular injections into the monkeys and by subcutaneous injections into the human. Excretion of tritium labelled products were followed in urine (in both species) and feces (in monkeys only) and several metabolites were identified by GC/MS. The analogues were found to be resistant to the 15-hydroxy dehydrogenase and furthermore the degradation by β-oxidation was delayed. About 13% of the given dose of 15-methyl-Δ4-cis-PGF1α was excreted unchanged into urine and feces from the monkey. The corresponding figure for 16,16-dimethyl-Δ4-cis-PGF1α was about 20%. In addition, a large part of the metabolites had the carbon skeleton intact and were only metabolized by ω-oxidation. The relative resistance to degradation of these two analogues is likely to be the basis for their prolonged pharmacological activity. © 1979.