Determination of diphenhydramine in rat milk and plasma and its effects on milk composition and mammary gland nucleic acids.
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.
Dostal
L A
LA
National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Schwetz
B A
BA
D000818:Animals; D004247:DNA / Q000032:analysis; D004155:Diphenhydramine / Q000032:analysis* / Q000097:blood; D005260:Female; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism*; D008892:Milk / Q000032:analysis*; D009696:Nucleic Acids / Q000187:drug effects / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D009696:Nucleic Acids; D012313:RNA; D004155:Diphenhydramine; D004247:DNA