地非三唑与甾体激素类药物的体外相互作用

目的观察地非三唑与甾体激素类药物的代谢性相互作用，为临床合理用药提供科学依据。方法选择在临床上可能与地非三唑合用的甾体激素类药物，如米非司酮、雌二醇、醋酸甲羟孕酮、黄体酮和炔诺酮等进行试验。分别将它们与地非三唑在鼠肝微粒体中共孵育，采用反相高效液相色谱法测定孵育液中地非三唑和共孵育药物的剩余浓度或代谢产物浓度，计算代谢抑制常数值。结果地非三唑对米非司酮、雌二醇、醋酸甲羟孕酮、黄体酮以及炔诺酮的代谢抑制常数K_i分别为(201.3±1.0)，(94±4)，(128.7±2.2)，(64±5)和(80±4) μmol·L^-1；雌二醇、醋酸甲羟孕酮、黄体酮以及炔诺酮对地非三唑的代谢抑制常数K_i分别为(66.9±2.2)，(60.0±2.3)，(163±10)和(88±5) μmol·L^-1。结论地非三唑与甾体激素类药物之间均有不同程度的代谢相互抑制作用。

In vitro metabolic interaction between diphenytriazol and steroid hormone drugs

AIM: To observe the metabolic interaction between diphenytriazol and steroid hormone drugs, and provide some useful information for clinical medication. METHODS: The 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. RESULTS: The 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. CONCLUSION: Diphenytriazol shows metabolism interaction with steroid hormone drugs such as estradiol, medroxyprogesterone acetate, progesterone and norethisterone.