Comparison of the pharmacokinetics of verapamil in the pregnant and non-pregnant rabbit: study of maternal and foetal tissue levels

1. The comparison of the pharmacokinetics of verapamil (TIER) has been stud ied between the non-pregnant and pregnant rabbit following VER intravenous (i.v.) bolus administration. Also studied has been VER tissue distribution in the non-Dregnant and pregnant rabbit and its foetuses following an i.v. infusion of VER. 2. When the pharmacokinetic variables were compared between the pregnant an d non pregnant rabbit, it was observed that t(1/2)lambda(z), V-1 and V-D we re significantly higher in the non-pregnant than in the pregnant rabbit. Mo reover, lambda(z), was significantly lower in the nonpregnant than in the p regnant rabbit. However, AUC and CL showed no significant differences betwe en the pregnant and non-pregnant rabbit. 3. When tissue concentrations were examined, it was found that in most of t he tissues studied high concentrations of VER were found both in the pregna nt and non-pregnant rabbit. Furthermore, VER concentrations in the uterus, heart, spleen and kidney were significantly higher in the non-pregnant than in the pregnant rabbit. 4. The results suggest that VER diffuses poorly through the placenta, given that VER blood concentrations were lower in blood foetuses than in materna l blood. Moreover, the concentrations of VER in the selected foetal tissues were either similar (brain and liver) or lower than those observed in mate rnal tissues.