Influence of the estrus cycle of the mouse on the disposition of SHetA2 after vaginal administration.
Influence of the estrus cycle of the mouse on the disposition of SHetA2 after vaginal administration.
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DOI：
10.1016/j.ejpb.2018.07.004
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Garcia-Contreras L
中科院分区：
文献类型：
--
作者：
Mahjabeen S;Hatipoglu MK;Benbrook DM;Kosanke SD;Garcia-Contreras D;Garcia-Contreras L
SHetA2 is novel compound with the potential to treat cervical dysplasia, but has poor water solubility. A vaginal suppository formulation was able to achieve therapeutic concentrations in the cervix of mice, but these concentrations were variable. Histological analysis indicated that mice in the same group were in different stage of their estrous cycle, which is known to induce anatomical changes in their gynecological tissues. We investigated the effect of these changes on the pharmacokinetics and pharmacodynamics of SHetA2 when administered vaginally. Mice were synchronized to be either in estrous or diestrus stage for administration of the SHetA2 suppository. Pharmacokinetic parameters were calculated from the SHetA2 concentrations vs. time data. The reduction in the expression of cyclin D1 protein in the cervix was used as pharmacodynamic endpoint. Mice dosed during diestrus had a larger AUCcervix (335 μg.mL.h−1), higher Cmax (121.8 ± 38.7 μg/g) and longer t1/2-cervix (30.3 h) compared to mice dosed during estrus (120 μg.mL.h−1, 44.6 ± 29.5 μg/g and 3.6 h respectively). Therapeutic concentrations of SHetA2 were maintained for 48 h in the cervix of mice dosed during diestrus and for only 12 h in the estrus group. The treatment reduced the expression of cyclin D1 protein in the cervix of mice in the estrus to a larger extent. These results indicate that the estrous cycle of mice influences significantly the disposition of SHetA2 after vaginal administration and may also influence its efficacy.
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影响因子：
5.4
作者：
ARBEIT, JM;MUNGER, K;HANAHAN, D
通讯作者：
HANAHAN, D
DOI：
10.3791/4389
发表时间：
2012-09-15
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
McLean AC;Valenzuela N;Fai S;Bennett SA
通讯作者：
Bennett SA
影响因子：
2.6
作者：
Kabirov, Kasim K.;Kapetanovic, Izet M.;Lyubimov, Alexander V.
通讯作者：
Lyubimov, Alexander V.
细胞周期蛋白D1降解的调节：在癌症发展中的作用和治疗发明的潜力。
影响因子：
37.3
作者：
Alao, John P.
通讯作者：
Alao, John P.
影响因子：
3.7
作者：
Byers SL;Wiles MV;Dunn SL;Taft RA
通讯作者：
Taft RA