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 (VER) has been studied between the non-pregnant and pregnant rabbit following VER intravenous (i.v.) bolus administration. Also studied has been VER tissue distribution in the non-pregnant and pregnant rabbit and its foetuses following an i.v. infusion of VER. 2. When the pharmacokinetic variables were compared between the pregnant and non-pregnant rabbit, it was observed that t(1/2)lambda2 V1 and V(D) were significantly higher in the non-pregnant than in the pregnant rabbit. Moreover, lambda(z) was significantly lower in the non-pregnant than in the pregnant rabbit. However, AUC and CL showed no significant differences between the pregnant and non-pregnant rabbit. 3. When tissue concentrations were examined, it was found that in most of the tissues studied high concentrations of VER were found both in the pregnant 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 maternal blood. Moreover, the concentrations of VER in the selected foetal tissues were either similar (brain and liver) or lower than those observed in maternal tissues.
Solans
C
C
Department of Pharmacology, Faculty of Veterinary Science, University of Zaragoza, Spain.
Bregante
M A
MA
Aramayona
J J
JJ
Fraile
L J
LJ
Garcia
M A
MA
D000465:Algorithms; D000818:Animals; D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011817:Rabbits; D014018:Tissue Distribution; D014700:Verapamil / Q000008:administration & dosage / Q000493:pharmacokinetics*
D002121:Calcium Channel Blockers; D007202:Indicators and Reagents; D014700:Verapamil