PHARMACOKINETICS OF VASOACTIVE SUBSTANCES ADMINISTERED INTO THE HUMANCORPUS CAVERNOSUM

The pharmacokinetics of vasoactive substances injected into the corpus cavernosum for the treatment of erectile dysfunction have not been in vestigated to date. We measured the local intracavernous and periphera l venous concentration curves of papaverine and prostaglandin E1, and its primary metabolite 15-keto-13,14-dihydro-prostaglandin E1 in an in tra-individual comparison after intracavernous injection. Papaverine w as measured with high performance liquid chromatography and prostaglan din E1 was measured with a specially adapted radioimmunoassay. The res ults demonstrate that papaverine is slowly draining into the systemic circulation, showing slightly elevated levels in the peripheral blood 30 and 60 minutes after injection. Prostaglandin E1 shows a much faste r decrease in local concentrations with no measurable increase in the periphery, probably due to the short half-time after lung passage. Mea surement of the primary metabolite proves a local degradation of prost aglandin E1 in the corpus cavernosum into the biologically inactive 15 -keto-13,14-dihydro-prostaglandin E1, which also shows a slight increa se in the peripheral circulation due to the longer half-time of approx imately 8 minutes. The data provide good explanation for the clinical finding of a markedly decreased incidence of priapism with the use of prostaglandin E1, which can be shown to be locally metabolized, compar ed to papaverine, which is retained in the corpus cavernosum in cases of nonvenogenic impotence.