Kinetic studies and production rate of equine (e) FSH in ovariectomized pony mares. Application to the determination of a dosage regimen for eFSH in a superovulation treatment

Abstract

The appropriate dosage regimen for equine FSH (eFSH) (dose, dosing interval) administration in a superovulation treatment in pony mares was determined by a kinetic approach using production rates and kinetic parameters of elimination of the hormone. Two dosage regimens were then tested in superovulation protocols. The eFSH production rates were determined by sampling four ovariectomized pony mares every 10 min for 8 h during the breeding season. Kinetic parameters were determined by administering four dose levels of a preparation of eFSH (4.4, 8.8, 17.6 and 35.2 μg/kg) by the i.v. route to the same mares, in a randomized 4 × 4 Latin Square protocol. The overall mean plasma clearance was 0.256 ± 0.07 ml.kg-1.min-1, and was independent of the dose. The mean residence time ranged from 5.5 to 10.8 h and increased with the dose. The estimated FSH production rates were 8.6 to 15.3 μg.kg-1.day-1 (i.e. 2.89 to 3.45 mg per day per mare). Two dosage regimens of eFSH were then tested in cyclic mares (ten treated mares in each trial): 3.45 mg per day (4.4 μ g/kg three times a day by the i.v. route), which corresponds to the maximal daily production rate of the native hormone in ovariectomized mares, and 1.72 mg per day (2.2 μg/kg three times a day), which corresponds to half of that production rate. The dosage regimen of 2.2 μg/kg three times a day gave satisfactory results in terms of efficacy (numbers of ovulations and embryos) with minimal unwanted effects (luteinized or anovulatory follicles). © 2004 Society for Endocrinology.