Dostal L A, Schwetz B A
National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
J Pharm Sci. 1989 May;78(5):423-6. doi: 10.1002/jps.2600780516.
To study the excretion of diphenhydramine into rat milk, milk and plasma concentrations of diphenhydramine were determined in lactating rats after single or multiple oral doses. Four hours after a single dose of 40 or 100 mg/kg of diphenhydramine, milk concentrations of the drug averaged 0.30 and 2.2 micrograms/mL, respectively, in two experiments, and the milk:plasma ratios ranged from 4.4 to 7.5. Multiple doses did not significantly affect the plasma or milk concentrations or the milk:plasma ratios, which were similar to the theoretical milk:plasma ratio based on pH partitioning for this compound (i.e., 4.0). Although the concentration of diphenhydramine was higher in milk than in plasma, the estimated dose received by the pups (0.057 mg/kg/d) based on the milk concentrations was much lower than that given to the mother. Oral diphenhydramine treatment at doses which significantly reduced maternal food consumption had no effect on milk solid, lipid, protein, or lactose concentrations, nor on mammary gland RNA or DNA content, indicating that diphenhydramine did not adversely affect lactation.
为研究苯海拉明在大鼠乳汁中的排泄情况，对哺乳期大鼠单次或多次口服给药后，测定了其乳汁和血浆中苯海拉明的浓度。在两个实验中，单次给予40或100mg/kg苯海拉明后4小时，乳汁中药物浓度平均分别为0.30和2.2μg/mL，乳汁与血浆浓度比在4.4至7.5之间。多次给药并未显著影响血浆或乳汁浓度以及乳汁与血浆浓度比，这些比值与基于该化合物pH分配的理论乳汁与血浆浓度比（即4.0）相似。尽管乳汁中苯海拉明的浓度高于血浆，但根据乳汁浓度估算幼崽摄入的剂量（0.057mg/kg/d）远低于给予母鼠的剂量。口服苯海拉明剂量显著降低母鼠食物摄入量时，对乳汁中的固体、脂质、蛋白质或乳糖浓度以及乳腺RNA或DNA含量均无影响，表明苯海拉明对泌乳没有不利影响。
