Metabolism and pharmacokinetics of prostaglandin analogs in man

Abstract

The metabolism of naturally occurring primary Prostaglandins was studied in several species during the 1960s. The investigations demonstrated that the metabolic degradation of these, biologically very potent, compounds was extremely rapid. The first step is an oxidation at carbon 15 in the Prostaglandin molecule leading to biologically inactive metabolites which are then further degraded. The half-life in the human circulation of primary Prostaglandins, e.g. PGE₂ and PGF_2α, has been estimated to be 5–10 s (cf. Samuelsson et al., 1975). The enzymes responsible for this rapid inactivation seem to appear in essentially all mammalian tissues (Samuelsson et al., 1975; Änggard et al., 1971). These studies led to efforts to synthesize Prostaglandin analogs where this oxidation at carbon 15 was blocked, which created compounds with a longer duration of biological action than the natural Prostaglandins.