Kylmälä T, Castrén-Kortekangas P, Seppänen J, Ylitalo P, Tammela T L
Division of Urology, Tampere University Hospital, Finland.
Pharmacol Toxicol. 1996 Sep;79(3):157-60. doi: 10.1111/j.1600-0773.1996.tb00260.x.
Estramustine phosphate is generally used as a second-line treatment in patients with advanced prostate cancer. The bone metastases due to the cancer are often treated simultaneously with clodronate in order to relieve the bone pain. Therefore, the interaction of clodronate (800 mg orally four times daily) and estramustine phosphate (280 mg orally twice daily) on their bioavailability was studied in twelve patients with prostate carcinoma and bone metastases. The drugs were first given separately, each to six patients, for five days, and then concomitantly for the same period. The bioavailabilities of the drugs were calculated on the last day of each treatment period. When clodronate was given alone, its concentrations in serum and AUC for one dose interval (6 hr) did not differ from those obtained with the drug given concomitantly with estramustine phosphate, nor did the combination of estramustine phosphate change the excretion of clodronate in urine. The serum concentrations of estramustine phosphate were elevated by about 80% when the drug was given together with clodronate. The AUC for one dose interval (12 hr) was also significantly higher for estramustine phosphate with clodronate than without clodronate. The urinary excretion of estrone, a major metabolite of estramustine phosphate, was also significantly higher after the admission with clodronate. The results suggest that clodronate increases the oral bioavailability of estramustine phosphate.
磷酸雌莫司汀一般用作晚期前列腺癌患者的二线治疗药物。对于因癌症导致的骨转移，常同时使用氯膦酸盐进行治疗以缓解骨痛。因此，在12例患有前列腺癌并伴有骨转移的患者中，研究了氯膦酸盐（每日口服4次，每次800毫克）和磷酸雌莫司汀（每日口服2次，每次280毫克）对彼此生物利用度的相互作用。药物首先分别给予6例患者，各服用5天，然后同时服用相同疗程。在每个治疗期的最后一天计算药物的生物利用度。单独给予氯膦酸盐时，其血清浓度和一个剂量间隔（6小时）的AUC与与磷酸雌莫司汀同时给药时获得的结果无差异，磷酸雌莫司汀的联合使用也未改变氯膦酸盐的尿排泄。当磷酸雌莫司汀与氯膦酸盐一起给药时，其血清浓度升高约80%。与未使用氯膦酸盐相比，与氯膦酸盐联用的磷酸雌莫司汀一个剂量间隔（12小时）的AUC也显著更高。氯膦酸盐给药后，磷酸雌莫司汀的主要代谢产物雌酮的尿排泄也显著增加。结果表明，氯膦酸盐可提高磷酸雌莫司汀的口服生物利用度。
