The follicle-stimulating hormone (FSH) analog corifollitropin alfa (Org 36286) is a potent FSH receptor agonist with an extended plasma half-life due to the fusion of the carboxy-terminal peptide (CTP) of the human chorionic gonadotropin beta-subunit and the human FSH beta-subunit. The absorption, tissue distribution, metabolism and excretion of corifollitropin alfa were studied in rats following a single subcutaneous administration of [(125)I]corifollitropin alfa. The biological activity of [(125)I]corifollitropin alfa was confirmed by an in vitro FSH receptor transactivation assay. Radioactivity in blood, serum, tissues and excreta was determined by radiometry up to 168 h post dosage. A drug-specific distribution occurred mainly to ovaries and the renal system. The distribution was similar in albino and pigmented rats, ruling out effects of melanin binding on distribution. Metabolites were studied in urine and serum by SDS-PAGE. The maximum concentration of 12 h indicated a slow absorption and excretion. Radioactivity was mainly (86%) excreted via urine. 90% of the radioactivity in serum was identified as [(125)I]corifollitropin alfa, whereas only 7-15% of the radioactivity in urine was identified as [(125)I]corifollitropin alfa and its dissociation products, the alpha- and beta-subunits (including its CTP part). The remainder of the radioactivity in either matrix represented low-molecular-weight compounds resulting from catabolism and deiodination. In conclusion, the metabolic fate of corifollitropin alfa strongly resembles that of endogenous glycoprotein hormones, which predominantly consists of kidney clearance and the urinary excretion of the intact protein in parallel to kidney catabolism.
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