Pharmacokinetics of vasoactive substances administered into the human corpus cavernosum

The pharmacokinetics of vasoactive substances injected into the corpus cavernosum for the treatment of erectile dysfunction have not been investigated to date. We measured the local intracavernous and peripheral venous concentration curves of papaverine and prostaglandin E1, and its primary metabolite 15-keto-13,14-dihydro-prostaglandin E1 in an intra-individual comparison after intracavernous injection. Papaverine was measured with high performance liquid chromatography and prostaglandin E1 was measured with a specially adapted radioimmunoassay. The results 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 faster decrease in local concentrations with no measurable increase in the periphery, probably due to the short half-time after lung passage. Measurement of the primary metabolite proves a local degradation of prostaglandin E1 in the corpus cavernosum into the biologically inactive 15-keto-13,14-dihydro-prostaglandin E1, which also shows a slight increase in the peripheral circulation due to the longer half-time of approximately 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, compared to papaverine, which is retained in the corpus cavernosum in cases of nonvenogenic impotence.