Administration of antiprogestin J956 for contraception in bears: A pharmacological study

Effective and reversible control of reproduction in bears is highly desirab le for conservation and management programs in zoos to establish geneticall y variable ex-situ populations of bears within the constraints of limited s pace in captivity. The reproductive physiology of bears is characterized by two main traits-seasonality and delayed implantation, which is progesteron e dependent, This offers the opportunity to interrupt early pregnancy by sh ort-term administration of antiprogestins. The aim of the present study was to investigate the pharmacological charact eristics of antiprogestin J956 to establish an efficient contraceptive prot ocol for administration of J956 in captive bears. The J956 binds to the ute rine progesterone receptor of bears (n=2) with almost the same relative bin ding affinity (1.25) as progesterone. The blood serum level of J956 after o ral (on four consecutive days) and single parenteral administration was det ermined by a modified progestin receptor assay. The relative bioavailabilit y of J956 after oral administration was approximately 10% of the parenteral administration. The estimated half-life was 12 to16 hours after oral admin istration. Parenteral treatment of J956 (10 mg/kg body mass) led to sustain plasma concentrations (6.4 +/-1.3 ng/mL) in one black bear and in five bro wn bears, The plasma level lasted for almost 2 months. Oral and low dosage parenteral (I mg/kg body mass) administration of J956 had no effect on ongo ing pregnancies in bears. Whereas single parenteral administration with hig her dosages of J956 (7.5 to 10 mg,kg body mass) efficiently prevented impla ntation of early embryos in eight female captive bears. (C) 2001 by Elsevie r Science Inc.