title: Pharmacokinetics of cimetidine during lactation: species differences in cimetidine transport into rat and rabbit milk.
abstract: The disposition of cimetidine, including transfer into milk, was characterized in the rabbits and rats. Nursing rabbits and suckling offspring exhibited similar pharmacokinetics with a mean systemic disease (CL) in the adults and pups of 22.0 +/- 5.2 and 30.4 +/- 8.9 ml/min/kg, respectively. Cimetidine exhibited a distributional time lag and a prolonged T 1/2 in milk compared to serum (70 +/- 15 vs. 33 +/- 5 min), resulting in a time-dependent milk to serum (M/S) drug concentration ratio. The ratio of the area under the time curve of cimetidine in serum and milk was 1.49 +/- 0.37 and was comparable to a diffusional model predicted M/S ratio of 1.16 +/- 0.11. Unbound CL after a high cimetidine infusion regimen (16.6 +/- 7.3 ml/min/kg) was significantly less than that after two lower infusion rates (26.2 +/- 4.9 and 29.4 +/- 12.3 ml/min/kg, respectively). M/S determined at increasing steady-state serum concentrations were 1.03, 1.08 and 1.08, respectively, which agreed well with the corresponding predicted M/S (1.06, 1.14 and 1.13, respectively). Cimetidine was also administered to lactating rats and resulted in a concentration-dependent decrease in CL (11.2 +/- 1.5, 10.8 +/- 2.7 and 7.30 +/- 1.0 ml/min, respectively) after three increasing infusion rates. The steady-state M/S ratio decreased slightly from 31.9 +/- 9.0 to 26.5 +/- 9.5 and 24.6 +/- 6.4 with the increasing infusion rate. Steady-state M/S values were 6-fold higher than the predicted M/S value (4.19). Hence, cimetidine transport into rabbit milk appears to be governed by diffusion, whereas cimetidine transfer into rat milk may involve active transport.
authors.affiliation: Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington.
authors.forename: P J
authors.initials: PJ
authors.lastname: McNamara
authors.forename: D
authors.initials: D
authors.lastname: Burgio
authors.forename: S D
authors.initials: SD
authors.lastname: Yoo
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002927:Cimetidine / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006863:Hydrogen-Ion Concentration; D007262:Infusions, Intravenous; D007774:Lactation / Q000378:metabolism*; D008892:Milk / Q000032:analysis*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
chemical_list: D002927:Cimetidine