Pharmacokinetics of eCG and induction of fertile estrus in bitches using eCG followed by hCG
Pharmacokinetics of eCG and induction of fertile estrus in bitches using eCG followed by hCG
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DOI：
10.1016/j.theriogenology.2012.04.012
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发表时间：
2012-09-15
期刊：
影响因子：
2.8
通讯作者：
Stornelli, M. A.
中科院分区：
文献类型：
--
作者：
Stornelli, M. C.;Garcia Mitacek, M. C.;Stornelli, M. A.
目的是设计一种结合eCG和hCG的方案来诱导母狗的发情。实验1,3只切除卵巢子宫的母狗进行1万IU的心电图iv， 15天后进行1万IU的心电图im。每次注射后144小时采集血样，测量心电图浓度。在实验2中，25只健康、完整的晚期失情母狗被分配到5种剂量的eCG（5、10、15、20、44或50 IU/kg eCG； [TRT5-TRT50]）中的一种。在eCG给药前、每隔一天或连续14天采集性行为（SB）、发情临床体征（CSE）和阴道细胞学（VC）样本并评分。实验3，将完整的晚期哺乳期母狗分为治疗组（TRT, n = 16）， 7 d后进行心电图（50 IU/kg）和绒毛膜促性腺激素（500 IU/kg）检查；或安慰剂组（PLA; n = 8），他们每天接受1 mL生理盐水溶液。所有被诱导发情的母狗都用新鲜精液进行交配或AT。在实验1中，im和iv两种途径的最大观察浓度（C-max） eCG相似（6.1 +/- 0.9 vs. 8.6 +/- 0.5 IU/mL, P < 0.08），而im比iv途径的最大观察浓度（T-max）时间更长（17.5 +/- 0.5 vs. 11.6 +/- 0.3 h, P < 0.01）。静脉注射和静脉注射途径的曲线下面积（AUC）相似（P < 0.48），两种途径的血清中至少144小时可检测到心电图。试验2、治疗后3 d和治疗后3 ~ 5 d， TRT50组所有母狗得分均高于TRT5-44组（P < 0.01）。在TRT50中，从治疗到发情的平均间隔为4.0 +/- 0.4天。实验3中，TRT组治疗至发情的平均间隔时间较PLA组短（4.1 +/- 3.3 vs. 68.5 +/- 4.4 d, P < 0.01）。TRT组和PLA组以前的发情期间隔相似（199.6 +/- 7.2 vs. 197.5 +/- 10.2天），但TRT组新的发情期间隔比PLA组短（164.0 +/- 7.2 vs. 212.2 +/- 10.2天；间隔相互作用治疗，P < 0.007）。TRT治疗后第1天血清P-4浓度升高（0.7 +/- 0.3 vs. 22.8 +/- 4.2 ng/mL, P < 0.01）；而PLA无明显变化（P < 0.84）。94%的动物是人工饲养的（15/16;Al, n = 7；自然交配，n = 8）， 80%（12/15）怀孕。所有母狗都没有心电图和绒毛膜促性腺激素治疗的副作用。我们得出结论：50iu /kg eCG联合500 IU hCG可有效诱导母狗在发情后164天正常发情和可育发情，受孕率达80%，无副作用，发情间隔缩短48天。(c) 2012年Elsevier Inc.出版
The aim was to design a protocol combining eCG followed by hCG for estrus induction in the bitch. In Experiment 1, three ovariohysterectomized bitches received 10 000 IU of eCG iv, and 15 days later 10 000 IU of eCG im. Blood samples were taken up to 144 h after each injection to measure eCG concentrations. In Experiment 2, 25 healthy, intact late anestrous bitches were assigned to one of five doses of eCG (5, 10, 15, 20, 44, or 50 IU/kg eCG im; [TRT5-TRT50]). Sexual behavior (SB), clinical signs of estrus (CSE) and vaginal cytology (VC) samples were obtained and scored before eCG administration and every other day until onset of estrus, or for 14 days. In Experiment 3, intact late anestrous bitches were assigned to a treatment group (TRT; n = 16) and received eCG (50 IU/kg im) followed by hCG (500 IU im) 7 days later; or to a placebo group (PLA; n = 8) where they received 1 mL saline solution im. All bitches that were induced in estrus were mated or AT with fresh semen. In Experiment 1, maximum observed concentration (C-max) eCG were similar between im and iv routes (6.1 +/- 0.9 vs. 8.6 +/- 0.5 IU/mL, P > 0.08), whereas time for maximum observed concentration (T-max) was longer for im compared to iv routes (17.5 +/- 0.5 vs. 11.6 +/- 0.3 h, P < 0.01). The area under the curve (AUC) was similar for im and iv routes (P > 0.48), and eCG was detectable in serum for at least 144 h for both routes. In Experiment 2, 3 days or 3 to 5 days after treatment, all bitches in TRT50 had higher scores compared to TRT5-44 animals (P < 0.01). In TRT50, the mean interval from treatment to estrus was 4.0 +/- 0.4 days. In Experiment 3, the mean interval from treatment to estrus was shorter in the TRT group compared to the PLA group (4.1 +/- 3.3 vs. 68.5 +/- 4.4 days, P < 0.01). The previous interestrus interval was similar for TRT and PLA groups (199.6 +/- 7.2 vs. 197.5 +/- 10.2 days), but the new interestrus interval was shorter for the TRT compared to the PLA group (164.0 +/- 7.2 vs. 212.2 +/- 10.2 days; treatment by interval interaction, P < 0.007). Serum P-4 concentrations increased on the first day of cytologic diestrus after treatment in bitches in TRT (0.7 +/- 0.3 vs. 22.8 +/- 4.2 ng/mL; P < 0.01); but did not change in PLA (P > 0.84). Ninety-four percent of animals were bred (15/16; Al, n = 7; natural mating, n = 8), and 80% (12/15) became pregnant. None of the bitches had any side effects from the eCG and hCG therapy. We concluded that 50 IU/kg of eCG combined 7 days later with 500 IU of hCG was effective to induce normal and fertile estrus in bitches at 164 days post estrus, with an 80% pregnancy rate, with no side effects, and with a reduction of 48 days of the interestrus interval. (c) 2012 Published by Elsevier Inc.