Partlow E S, Campbell N R, Chan S C, Pap K M, Granberg K, Hasinoff B B
Department of Medicine, Foothills Hospital, Calgary, Alberta, Canada.
Clin Pharmacol Ther. 1996 Apr;59(4):389-93. doi: 10.1016/S0009-9236(96)90106-X.
A series of randomized crossover studies were performed to determine whether there was a reduction in serum levels of cimetidine and famotidine when coingested with ferrous sulfate (300 mg). Coingestion of a ferrous sulfate tablet with cimetidine (300 mg) was associated with little reduction in serum cimetidine area under the curve (AUC) (mean versus mean, 20.8 versus 23.4 mumol.hr/L; mean percentage difference, -11%; 95% confidence interval [CI] of percentage difference, -26% to 4.2%) or peak concentration (Cmax) (mean versus mean, 5.1 versus 6.1 mumol/L; mean percentage difference, -16%; CI of percentage difference, -36% to 4%). Similarly, ferrous sulfate solution coingested with cimetidine caused little change in cimetidine AUC (mean versus mean, 19.9 versus 23.0 mumol.hr/L; mean percentage difference, -13%; CI of percentage difference, -34% to 7%) or Cmax (mean versus mean, 5.0 versus 5.0 mumol/L; mean percentage difference, 1%; CI of percentage difference, -18% to 20%). Concurrent ingestion of famotidine (40 mg) with a ferrous sulfate tablet did not result in significant reductions in serum famotidine AUC (mean versus mean, 1.78 versus 1.99 mumol.hr/L; mean percentage difference, -10%; CI of percentage difference, -34% to 13%) or Cmax (mean versus mean, 0.31 versus 0.32 mumol/L; mean percentage difference, -3%; CI of percentage difference, -27% to 22%). The formation of famotidine:iron(III) complexes was shown in methanol but was not observed in an aqueous buffer at pH 6.5. Ranitidine did not bind iron in an aqueous buffer and only weakly bound iron in methanol. Coingestion of ferrous sulfate with either cimetidine or famotidine does not cause a clinically relevant reduction in serum histamine H2-receptor blocker levels and, on the basis of in vitro binding experiments, iron is unlikely to interact with ranitidine.
进行了一系列随机交叉研究，以确定西咪替丁和法莫替丁与硫酸亚铁（300毫克）同时服用时，其血清水平是否会降低。硫酸亚铁片与西咪替丁（300毫克）同时服用时，血清中西咪替丁曲线下面积（AUC）降低很少（均值对比，20.8对23.4微摩尔·小时/升；平均百分比差异，-11%；百分比差异的95%置信区间[CI]，-26%至4.2%）或峰浓度（Cmax）（均值对比，5.1对6.1微摩尔/升；平均百分比差异，-16%；百分比差异的CI，-36%至4%）。同样，硫酸亚铁溶液与西咪替丁同时服用时，西咪替丁AUC变化很小（均值对比，19.9对23.0微摩尔·小时/升；平均百分比差异，-13%；百分比差异的CI，-34%至7%）或Cmax（均值对比，5.0对5.0微摩尔/升；平均百分比差异，1%；百分比差异的CI，-18%至20%）。法莫替丁（40毫克）与硫酸亚铁片同时服用不会导致血清中法莫替丁AUC显著降低（均值对比，1.78对1.99微摩尔·小时/升；平均百分比差异，-10%；百分比差异的CI，-34%至13%）或Cmax（均值对比，0.31对0.32微摩尔/升；平均百分比差异，-3%；百分比差异的CI，-27%至22%）。在甲醇中显示有法莫替丁：铁（III）络合物形成，但在pH值为6.5的水性缓冲液中未观察到。雷尼替丁在水性缓冲液中不与铁结合，在甲醇中仅与铁弱结合。硫酸亚铁与西咪替丁或法莫替丁同时服用不会导致血清中组胺H2受体阻滞剂水平出现临床相关降低，并且根据体外结合实验，铁不太可能与雷尼替丁相互作用。
