PROVIRON Tablet Ref.[51091] Active ingredients: Mesterolone

Following oral ingestion mesterolone is rapidly and almost completely absorbed in a dose range of 10-100 mg. The intake of Proviron generates maximum serum drug levels of 3,1 ± 1,1 ng/ml after 1,6 ± 0,2 hours.

Drug serum levels decrease with a terminal half-life of 12-13 hours. Mesterolone is bound to serum proteins by 98%. Binding to albumin accounts for 40% and binding to SHBG (sex hormone binding globulin) to 58%.

Mesterolone is rapidly inactivated by metabolism. The metabolic clearance rate from serum is 4,4 ± 1,6 ml.min^-1.kg^-1. There is no renal excretion of unchanged drug. The main metabolite has been identified as 1α-methyl-androsterone, which in conjugated form accounts for 55-70% of renally excreted metabolites. The ratio of main metabolite glucuronide to sulphate was about 12:1.

As a further metabolite 1α-metyl-5α-androstane-3α,17β-diol, has been recognized, which accounted for about 3% of renally eliminated metabolites. No metabolic conversion into estrogens or corticoids has been observed. In form of metabolites mesterolone is excreted by about 85% of dose with the urine and by about 14% of dose with the feces. Within 7 days 93% of dose was excreted, the half of which had been excreted with urine within 24 hours.

The absolute bioavailability of mesterolone was determined to about 3% of the oral dose.

The daily intake of Proviron 25 will lead to an about 30% increase in drug serum levels.

In systemic tolerance studies after repeated administration of Proviron no findings were observed which raise objections to its use at the doses required for therapy.

Experimental investigations into possible sensitizing effects of Proviron have not been carried out.

Investigations into embryotoxic effects have not been carried out with Proviron, since the preparation is prescribed for the therapeutic use in male patients. Fertility studies to clarify a possible deleterious effect on sperm cells have not been carried out with Proviron. On the basis of long-term systemic tolerance studies, these results do not indicate a toxic effect on sperm cells, but a central mediated inhibition of spermatogenesis. Although generally known in animal experiments, this effect has not been observed in humans even after years of usage at the recommended therapeutic dose levels.

Investigations into the mutagenic effect have not been carried out. On the basis of the negative results with other steroid hormones in in vitro and in vivo<.em> mutagenicity tests, no such potential is to be expected.

Systemic tolerance studies after repeated administration in rats and dogs over a period of 6 and 12 months did not produce any indications of a substance-related tumorigenic effect. Therefore, a further characterization with regard to a possible tumorigenic potential has not been carried out. However, it must be kept in mind that sex steroids can promote the growth of certain hormone dependent tissues and tumours.

On the whole, the results of toxicological investigations do not raise objections to the prescribed use of Proviron in humans for the indications and at the doses given.