Effect of chemical modifications on the metabolic transformation of prostaglandins

The metabolism of three analogues of PGF2alpha was studied in the Cynomolgus monkey and in the human, viz., 15-methyl-PGF2alpha, 16,16-dimethyl PGF2alpha, and 17-phenyl-18,19,20-trinor-PGF2alpha. The half-lives of the three compounds in the human circulation was considerably longer than that of PGF2alpha. The dehydrogenation of the secondary alcohol group at C-15 was completely blocked in the two first-mentioned compounds. These were degraded mainly by beta-oxidation, and their main metabolites, both in plasma and urine, were dinor-15-methyl-PGF2alpha and dinor-16,16-dimethyl-PFG2alpha, respectively. 17-Phenyl-18,19,20-trinor-PGF2alpha, finally, was metabolized to some extent by dehydrogenation at C-15, and also by reduction of the delta13 double bond and by beta-oxidation.