Pharmacokinetics of cimetidine during lactation: species differences in cimetidine transport into rat and rabbit

The disposition of cimetidine, including transfer into milk, was characterized in the rabbits and rats. Nursing rabbits and suck-ling 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 mI/mm/kg, respectively. Cimetidine exhibited a distil-butional time lag and a prolonged T#{189}in milk compared to serum (70 ± I 5 vs. 33 ± 5 mm), 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 1.1 6 ± 0.1 1. Unbound CL after a high cimetidine infusion regimen (1 6.6 ± 7.3 mI/mm/kg) was significantly less than that after two lower infusion rates (26.2 ± 4.9 and 29.4 ± 1 2.3 mI/ mm/kg, respectively). M/S determined at increasing steady-stat