Pharmacokinetics of verapamil in lactating rabbits. Prediction of verapamil distribution into rabbit milk

Gen Pharmacol. 2000 Apr;34(4):237-43. doi: 10.1016/s0306-3623(00)00066-5.

Abstract

In this work, we have studied the pharmacokinetics and milk penetration of verapamil following intravenous administration in lactating rabbits. Milk-to-serum drug concentration ratios (M/B(obs)) have been determined using area under the milk and serum concentration-time profiles, and the resulting values have then been compared with those obtained by theoretical classical diffusion milk transfer models that were described by Fleishaker et al. [J. Pharm. Sci. 76 (1987) 189.], Atkinson and Begg [Br. J. Clin. Pharmacol. 25 (1990) 495.], and Stebler and Guentert [Pharm. Res. 9 (1992) 1299.]. The pharmacokinetic profile of verapamil in lactating rabbits following endovenous administration is described in the form of a two-compartment model. Moreover, we detected an important milk transfer after endovenous administration of verapamil in lactating rabbits. M/B(obs) was near 15. The classical diffusional models mentioned were not able to predict this extensive transfer of verapamil into rabbit milk. However, when the classical Fleishaker equation was modified and a stepwise regression was carried out, we found that the M/B(obs) value could be predicted using the plasma and milk protein binding.

MeSH terms

  • Animals
  • Binding Sites
  • Calcium Channel Blockers / pharmacokinetics*
  • Female
  • Infusions, Intravenous
  • Lactation / metabolism*
  • Milk / chemistry*
  • Rabbits
  • Verapamil / pharmacokinetics*

Substances

  • Calcium Channel Blockers
  • Verapamil