Dostal L A, Weaver R P, Schwetz B A
National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina 27709.
Toxicol Appl Pharmacol. 1990 Mar 1;102(3):430-42. doi: 10.1016/0041-008x(90)90039-w.
The excretion of cimetidine and ranitidine into rat milk following single or multiple oral doses and the subsequent effects on their suckling pups and on milk composition and milk synthesis were investigated. Following a single dose of [3H]cimetidine, peak milk cimetidine concentrations were maintained from 1 until 4 hr, while plasma concentrations peaked at 10% of the milk level at 30 min and then declined. Multiple doses of cimetidine (18 or 180 mg/kg/day) on Days 13-16 of lactation led to milk cimetidine concentrations of 17 and 113 micrograms/ml. The milk/plasma ratios far exceeded the theoretical milk/plasma ratio of 2.0. Ranitidine concentrations in rat milk following ranitidine treatment (4.5 or 45 mg/kg/day) were also greater (6.8-15 times) than in plasma, but only slightly greater than the predicted ratio of 5.0. There were no changes in liver weight or in hepatic aminopyrine N-demethylase activity in the cimetidine- or ranitidine-treated dams or their pups. Cimetidine treatment had no effect on milk lipid, solid, or protein content, but at 180 mg/kg/day, caused a significant increase in milk lactose. The RNA/DNA ratio in the mammary gland was significantly increased by cimetidine, suggesting increased milk synthesis. Ranitidine had no effect on milk composition or on mammary gland RNA, DNA, or RNA/DNA. Therefore, high concentrations of cimetidine and ranitidine were excreted into rat milk, but no deleterious effects on the suckling pups, or the composition of the milk, or on the milk synthetic activity were observed.
研究了单次或多次口服西咪替丁和雷尼替丁后其在大鼠乳汁中的排泄情况，以及对其哺乳幼崽、乳汁成分和乳汁合成的后续影响。单次给予[³H]西咪替丁后，乳汁中西咪替丁浓度在1至4小时维持在峰值，而血浆浓度在30分钟时达到乳汁水平的10%峰值，随后下降。在哺乳期第13至16天多次给予西咪替丁（18或180毫克/千克/天），导致乳汁中西咪替丁浓度分别为17和113微克/毫升。乳汁/血浆比值远超过理论上的2.0乳汁/血浆比值。雷尼替丁治疗（4.5或45毫克/千克/天）后大鼠乳汁中的雷尼替丁浓度也高于血浆（6.8至15倍），但仅略高于预测的5.0比值。接受西咪替丁或雷尼替丁治疗的母鼠及其幼崽的肝脏重量和肝氨基比林N-脱甲基酶活性均无变化。西咪替丁治疗对乳汁脂质、固体或蛋白质含量无影响，但在180毫克/千克/天时，导致乳汁乳糖显著增加。西咪替丁使乳腺中的RNA/DNA比值显著增加，表明乳汁合成增加。雷尼替丁对乳汁成分或乳腺RNA、DNA或RNA/DNA无影响。因此，高浓度的西咪替丁和雷尼替丁排泄到大鼠乳汁中，但未观察到对哺乳幼崽、乳汁成分或乳汁合成活性有有害影响。
