Kottwitz Jack J, Kiso Wendy, Boothe Dawn M, Schmitt Dennis
College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
College of Veterinary Medicine, Auburn University, Auburn, AL 46849, USA.
Animals (Basel). 2022 Jul 21;12(14):1852. doi: 10.3390/ani12141852.
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.
孕酮及其衍生物是维持哺乳动物妊娠的关键激素。如果这些激素的水平降至维持妊娠所需的特定物种要求以下,妊娠终止(包括分娩或流产)将不可避免。合成孕激素烯丙孕素在美国被FDA批准用于抑制发情或同期发情,并且在黄体功能不足或孕酮水平异常低的情况下,可超适应症用于多种物种以维持妊娠。三头怀孕的亚洲象在妊娠晚期的第41至131天接受了烯丙孕素治疗,在烯丙孕素给药停止后的15至31天分娩。给两头未怀孕的亚洲象单次注射0.2mg/kg的烯丙孕素,提供了初步的药代动力学数据。使用超高效液相色谱-三重四极杆质谱联用仪(UPLC-MS)分析了三个临床病例中的两个以及两项初步研究大象的血清样本。样本数量少限制了分析;然而,确定了以下参数:AUC∞为635.4±73.8 ng*h/mL,Cmax为30.2±14.4 ng/mL,Tmax为4±2.8小时,末端T1/2为47.5±3.0小时,MRT为36.0 + 3.4小时,Vd/F为1243.8 + 275.0 L/kg。这些数据以及所描述的三个病例表明,烯丙孕素可作为外源性孕激素给予亚洲象,以支持内源性孕激素水平低的大象妊娠。