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Penetration of diltiazem into breast milk and its pharmacokinetics in the lactating rabbit

1. The aim was to investigate the milk transfer and pharmacokinetics of diltiazem (DTZ) in the lactating rabbit following DTZ intravenous (i.v.) administration. In addition, DTZ metabolism in mammary tissue and milk was also studied. 2. The pharmacokinetic parameters that largely determine drug disposition (AUC, V D, CL) showed no significant differences between the non-lactating and lactating rabbit. 3. When DTZ was administered to the lactating rabbit, the observed DTZ milk-to-blood AUC ratio (M/B) closely correlated with the calculated ratio, as predicted by a diffusional model, suggesting that DTZ passes into milk via non-ionic diffusion and that other factors which may affect the milk transfer seem to have limited relevance. 4. After a single intravenous dose of DTZ to the lactating rabbit, deacetyldiltiazem (M1) and demethyldiltiazem (MA) were observed in blood, but only M1 could be detected in milk. 5. In conclusion, DTZ seems to diffuse freely into milk after its i.v. administration to the lactating rabbit and should not be given to nursing mammals because of the potential risk for their young. This risk may be even higher because of the presence of M1 (a pharmacologically active metabolite) in milk after administration of the parent drug.