Administration of Altrenogest to Maintain Pregnancy in Asian Elephants (Elephas maximus)

SIMPLE SUMMARY: The Asian Elephant (Elephas maximus) is an IUCN (International Union of the Conservation of Nature) Endangered species that has interacted with humans for centuries. Despite advances in captive elephant breeding knowledge, worldwide populations continue to decline. Progesterone is a key reproductive hormone for the maintenance of pregnancy in mammalian species. The monitoring of serum progesterone levels has become a key method of management for captive breeding of elephants. The synthetic progesterone, altrenogest, has been administered to multiple species of mammals both for management of estrus and maintenance of pregnancy. This paper details three Asian elephant pregnancies maintained by the administration of altrenogest after endogenous progesterone levels decreased below the point needed to maintain pregnancy. Pharmacokinetic parameters of altrenogest administered orally as a single dose to nonpregnant pilot study elephants are presented as preliminary data on the administration of this drug to Asian elephants as a pharmacological means of maintaining pregnancy to term. ABSTRACT: Progesterone and progesterone derivatives are key hormones in pregnancy maintenance in mammalian species. Cessation of pregnancy, including birth or miscarriage, is certain if levels of these hormones drop below a given species-specific requirement necessary to maintain pregnancy. The synthetic progestin, altrenogest, is FDA-approved in the United States for suppression of estrus or synchronization and is administered extra-label to multiple species to maintain pregnancies in cases of luteal deficiency or otherwise abnormally low progesterone levels. Three pregnant Asian elephants received altrenogest from 41 to 131 days during the final trimester of pregnancy, with parturition occurring from 15 to 31 days after altrenogest administration stopped. A single dose of 0.2 mg/kg altrenogest administered to two nonpregnant Asian elephants provided pilot pharmacokinetic data. Serum samples from two of the three clinical cases and the two pilot study elephants were analyzed using Ultra Performance Liquid chromatography coupled to a triple quadruple mass spectrometer (UPLC-MS). Small sample numbers limited analysis; however, the following were determined: AUC∞ of 635.4 ± 73.8 ng*h/mL, Cmax of 30.2 ± 14.4 ng/mL at a Tmax of 4 ± 2.8 h, terminal T1/2 of 47.5 ± 3.0 h, MRT of 36.0 + 3.4 h and Vd/F of 1243.8 + 275.0 L/kg. These data and the three described cases serve as an indication that altrenogest can be administered to Asian elephants as an exogenous progestin to support pregnancy in elephant pregnancies with low endogenous progestin levels.