AIMTo observe the metabolic interaction between diphenytriazol and steroid hormone drugs, and provide some useful information for clinical medication.

METHODSThe steroid hormone drugs which may be co-administrated with diphenytriazol were selected, such as mifepriston, estradiol, medroxyprogesterone acetate, progesterone, norethisterone and so on. Diphenytriazol was incubated with each drug in rat liver microsome. The residual concentration of diphenytriazol or steroid hormone drugs in the microsomal incubates was determined by reversed-phase high-performance liquid chromatography, separately. The inhibition constants (K(i)) for each of them were calculated.

RESULTSThe inhibition constant K(is) of diphenytriazol for the metabolism of mifepristone, estradiol, medroxyprogesterone acetate, progesterone and norethisterone were (201.3 +/- 1.0), (94 +/- 4), (128.7 +/- 2.2), (64 +/- 5) and (80 +/- 4) micromol x L(-1), respectively. The inhibition constants K(i) of steroid hormone drugs for the metabolism of diphenytriazol was (66.9 +/- 2.2) micromol x L(-1) for estradiol, (60.0 +/- 2.3) micromol x L(-1) for medroxyprogesterone acetate, (163 +/- 10) micromol x L(-1) for progesterone and (88 +/- 5) micromol x L(-1) for norethisterone, respectively.

CONCLUSIONDiphenytriazol shows metabolism interaction with steroid hormone drugs such as estradiol, medroxyprogesterone acetate, progesterone and norethisterone.

Abortifacient Agents, Nonsteroidal ; metabolism ; pharmacology ; Abortifacient Agents, Steroidal ; metabolism ; Animals ; Contraceptives, Oral, Synthetic ; metabolism ; Drug Interactions ; Estradiol ; metabolism ; Female ; In Vitro Techniques ; Medroxyprogesterone ; metabolism ; Microsomes, Liver ; metabolism ; Mifepristone ; metabolism ; Rats ; Rats, Sprague-Dawley ; Triazoles ; metabolism ; pharmacology

OBJECTIVETo evaluate the clinical effect and safety of combined use of methotrexate and mifepristone for treatment of ectopic pregnancy.

METHODSBy searching in the major databases of CNKI, CBMdisk and Pubmed according to the criteria of evidence-based medicine, we collected data of randomized controlled trials pertaining to combined use of methotrexate and mifepristone in the treatment of ectopic pregnancy.

RESULTSTwenty-three randomized controlled trials involving totally 1 706 patients were collected according to the inclusion criteria, and meta-analysis of the data indicated that combined use of methotrexate and mifepristone can be of great value in the management of ectopic pregnancy in comparison with exclusive use of methotrexate [ combined odds ratio (OR) was 2.84 with 95%confidence interval [CI] (2.18, 3.69), Z=7.79, P<0.000 01].

CONCLUSIONThe clinical evidence derived from the analysis suggests that the combination of methotrexate and mifepristone for ectopic pregnancy management can be effective with good safety security and minimal side effects, but still, this conclusion needs further verification by randomized, double-blind, and controlled trials with larger sample size and more rigorous trial design.

Abortifacient Agents, Nonsteroidal ; administration & dosage ; Abortifacient Agents, Steroidal ; administration & dosage ; Adult ; Drug Therapy, Combination ; Female ; Humans ; Methotrexate ; administration & dosage ; Mifepristone ; administration & dosage ; Pregnancy ; Pregnancy, Ectopic ; drug therapy ; Randomized Controlled Trials as Topic ; Treatment Outcome

Primate placentation involves a series of cell proliferation, immigration and apoptosis which account for the progressive tissue remodelling at the implantation site. p53 is an important proto-oncogene involved in the regulation of cell-cycle and apoptosis. To study the effect of RU486 on apoptosis and expression of p53 at the fetal-maternal interface, the location of apoptotic cells and expression of p53 were examined using in situ 3'-end labeling method, immunohistochemistry and Western blot assay at the fetal-maternal interface of normal and RU486 treated rhesus monkey. Western blot analysis showed the specificity of the anti-human antibody used with the monkey tissue. In the placental villi, the apoptotic nuclei were observed mainly in the syncytiotrophoblast and part of the cytotrophoblast within the cell column; p53 protein was detected mainly in the cytotrophoblast. In the endometrium, positive signals for apoptosis and p53 were detected in some stromal cells. After two days of mifepristone treatment, the apoptotic cells increased significantly in both placental villi and endometrium. In the villi, the increased apoptotic nuclei were mainly localized to the cytotrophoblast. At the same time, p53-positive nuclei also increased in both villous cytotrophoblast cells and endometrial stromal cells, after the treatment of RU486. These results suggest that apoptosis and expression of p53 are essential in regulating trophoblastic homeostasis by controlling its proliferation in normal placenta, whereas the up-regulation of p53 protein may play an important role in apoptosis that happens at the fetal-maternal interface induced by RU486.
Abortifacient Agents, Steroidal ; pharmacology ; Animals ; Apoptosis ; drug effects ; Chorionic Villi ; pathology ; Female ; Macaca mulatta ; Mifepristone ; pharmacology ; Placentation ; drug effects ; physiology ; Pregnancy ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics

Abortifacient Agents, Steroidal ; administration & dosage ; Abortion, Induced ; methods ; Androgen Antagonists ; administration & dosage ; Contraceptives, Oral ; administration & dosage ; Female ; Fertilization in Vitro ; methods ; Gonadotropin-Releasing Hormone ; administration & dosage ; analogs & derivatives ; Hormone Replacement Therapy ; methods ; Hormones ; administration & dosage ; Humans ; Mifepristone ; administration & dosage ; Norpregnenes ; administration & dosage ; Pregnancy