Pharmacokinetic Behavior of Recombinant FSH Isohormones

Pharmacokinetic Behavior of Recombinant FSH Isohormones

The pharmacokinetic behavior of follitropin b and its isohormones was investigated in Beagle dogs that were given an intramuscular bolus injection of a number of FSH isohormone fractions, each with a specific pI value. With a decrease in pI value from 5.49 (basic) to 4.27 (acidic), the AUC increased and the clearance decreased, each more than 10-fold (Fig. 3). A more than twofold difference in elimination half-life between the most acidic and the most basic FSH isohormone fraction was calculated. The absorption rate of the two most acidic isoforms was higher than the absorption rates of all other isoforms. The AUC and the clearance for the follitropin b preparation, being a mixture of all isohormone fractions, corre-sponded with the centre of the isohormone profile (Fig. 3). In contrast, the elimination of the follitropin b preparation occurred at a rate similar to that of the most acidic fractions, indicating that the elimination rate is largely determined by the removal of the most acidic isoforms from the plasma.

Thus, for follitropin b isohormone fractions, a clear correlation exists between pI value and pharma-cokinetic behavior. Increasing acidity leads to an increase in the extent of absorption and elimination half-life and to a decrease in clearance.