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

BACKGROUNDLymphangioleiomyomatosis (LAM) is a rare disease that predominantly affects young females. It is considered as an "orphan" life-threatening disease of unknown etiology, with uncertain clinical prognosis, and no effective treatment. LAM can arise sporadically or in association with tuberous sclerosis complex (TSC), an autosomal inherited syndrome characterized by hamartoma-like tumor growth and pathologic features that are distinct from manifestations of pulmonary LAM. The clinical course of LAM is characterized by progressive dyspnea on exertion, recurrent pneumothorax, and chylous fluid collections.

METHODSFourteen cases of LAM from Zhongshan Hospital, Fudan University are reviewed, twelve were confirmed by lung biopsy, one by retroperitoneal lymphangioleiomyoma resection, and one by autopsy.

RESULTSAll 14 patients were women, aged 18 to 69 years (mean 43.3 years, median 46.5 years). Haemoptysis (57.1%) and chylothorax (35.7%) were more frequent than those described in previous case series. Extrapulmonary findings such as renal angiomyolipoma (AML), enlarged abdominal lymph nodes, liver AML and retroperitoneal lymphangioleiomyoma were seen in 21.4%, 14.3%, 7.14% and 7.14% in 14 cases respectively, which is remarkably lower than in the previously reported. Abnormal smooth muscle cells (LAM cells) were found to line the airways, bronchioles, lymphatics and blood vessels leading to airflow obstruction and replacement of the lung parenchyma by cysts. There were some surprises in the autopsy case as several LAM cell emboli were found in the veins of mediastinum lymph nodes; LAM cells were found to be disseminated in soft tissues adjacent to the ilium.

CONCLUSIONSWomen with unexplained recurrent pneumothorax, tuberous sclerosis, or a diagnosis of primary spontaneous pneumothorax or emphysema in the setting of limited or absent tobacco use should undergo high-resolution computed tomography (HRCT) scan screening for LAM. Routine abdominal and pelvic imaging examinations should be performed to detect extrapulmonary involvement. The autopsy studies histologically suggested that LAM could be a multisystemic disease and LAM cells might possess metastatic potential.

Adolescent ; Adult ; Aged ; Contraceptives, Oral, Synthetic ; Female ; Humans ; Immunohistochemistry ; Lymphangioleiomyomatosis ; diagnosis ; drug therapy ; metabolism ; pathology ; surgery ; Medroxyprogesterone ; therapeutic use ; Middle Aged ; Ovariectomy ; Progesterone ; therapeutic use ; Progestins ; therapeutic use ; Young Adult