Inhibition of lactation in the Beagle bitch with the prolactin inhibitor cabergoline (FCE 21336): Dose response and aspects of long-term safety.
Sixteen healthy, lactating Beagle bitches with litters of three to six pups were assigned to four treatment groups for one daily oral treatment of cabergoline in an oily solution (0, 1.25, 2.50 or 5.0 mcg/kg body weight (BW) for 5 d, commencing on Day 8 of lactation. Bitches and all their puppies were weighed daily for 2 d before treatments started, and for 10 d thereafter. Technicians rated daily treatment effects on maternal health, maternal behavior and mammary glands, using a scoring system. Treatments had no effect on maternal health, maternal body weight, and maternal behavior. Treatments with the two higher doses caused a reaction and a regression of the mammary glands in a dose-related fashion, resulting in cessation of lactation with 5 mcg/kg BW. Maternal treatment did not adversely affect the puppies' health, and no puppy was lost during the trial. However, average daily weight gains of puppies declined with increasing levels of cabergoline, causing significant weight losses in the 2.5 and 5 mcg/kg treatment group. This became evident after 2 d of treatment. To save the puppies in the highest dosage group, hand-feeding, and later, crossfostering, had to be used with all litters, starting on Day 3 or 4 of treatment. Weight losses were dose-related with an ED(50) of 1.5 mcg/kg/d and persisted for at least 24 h after treatment had ceased. Since puppies were left with their mothers to provide a continued suckling stimulus, lactation rebounded in all bitches treated with 2.5 mcg/kg, but only in two of four bitches treated with 5 mcg/kg. All bitches returned to estrus at their normal intervals. Fertility and fecundity at the next breeding were undisturbed.
Jöchle
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Wolfgang Jöchle Assoc., Inc., Denville, NJ 07834, USA.
Ballabio
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di Salle
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