MUSE Urethral Stick Ref.[8671] Active ingredients: Alprostadil

Approximately 80% of the alprostadil delivered by MUSE is absorbed through the urethral mucosa within 10 minutes. The half-life is less than 10 minutes and peripheral venous plasma concentrations are low or undetectable. Alprostadil is rapidly metabolised, both locally and in the pulmonary capillary bed; metabolites are excreted in the urine (90% within 24 hours) and the faeces. There is no evidence of tissue retention of alprostadil or its metabolites.

In rats, high doses of prostaglandin E₁ increased foetal resorption, presumably due to maternal stress. High concentrations of alprostadil (400 microgram/ml) had no effect on human sperm motility or viability in vitro. In rabbits, there was no foetal damage or effect on reproductive function at the maximum tested intravaginal dose of 4mg.

In the majority of in vitro and in vivo genotoxicity test systems in which alprostadil has been evaluated it produced negative results. These tests include the bacterial reversion test using Salmonella typhimurium, unscheduled DNA synthesis in rat primary hepatocytes, forward mutation assay at the hprt locus in cultured ovary cells from Chinese hamsters, alkaline elution test, sister chromatid exchange assay (all in vitro tests) and the micronucleus test in both mice and rats (in vivo tests). In two other in vitro tests, the mouse lymphoma forward mutation assay and the Chinese hamster ovary chromosomal aberration assay, alprostadil produced borderline positive and positive evidence, respectively, for chromosomal damage. In view of the number of negative in vitro results and the lack of evidence for genotoxicity in two in vivo tests, it is considered that the positive results obtained in these two in vitro tests are of doubtful biological significance. Overall the presently available evidence cannot fully exclude the risk of genotoxic activity in humans.