Active transport of cimetidine and ranitidine into the milk of Sprague Dawley rats

Diffusion determines the extent of accumulation into milk for most xenobiotics. However, cimetidine (CM) and ranitidine (RN) have been reported to accumulate to an extent greater than expected in rat and human milk, suggesting an active transport mechanism. In the present study, lactating Sprague Dawley rats were used in a random crossover design to characterize CM and RN active transport. Rat milk-to-serum ratios (MIS) (29.3 ± 3.2 vs. 13.0 ± 6.0; P <.05) and systemic clearance, Cl5 (12.9 ± 1.2 vs. 4.6 ± 1.0 mVmin, P <.05), were significantly reduced when exposed to a higher steady state infusion regi-men of CM (0.4 and 30 mglhr, respectively). By contrast, a infusion regimen of RN (0.4 and 30 mg/hr, respectively) pro-duced modest, but not statistically significant, reductions in M/S (12.7 ± 3.8 vs. 9.0 ± 2.6; P>.05) and Cl5 (12.2 ± 1.5 vs