Effects of pregnancy on the pharmacokinetics of lamotrigine in dogs.
OBJECTIVE
This study was designed to evaluate the effects of pregnancy on the kinetics of lamotrigine (LTG).


METHODS
Five pregnant dogs were given a daily dose of LTG (100 mg) for a period of 1 week. Two months after parturition, the same subjects were given the LTG dose (100 mg) over the same period. On both occasions, plasma LTG concentrations were determined by a sensitive, high-performance liquid chromatographic (HPLC) method, over a 30-h period after the last dose.


RESULTS
The mean maximum plasma concentration (Cmax), volume of distribution (Vd/F), and oral body clearance (Cl/F) for LTG (+/- SD) during pregnancy were 7.63+/-2.46 microg/ml 1.74+/-0.29 L/kg, and 0.19+/-0.04 L/h/kg, respectively. After pregnancy, the same variables were 6.12+/-2.24 microg/ml, 2.36+/-1.10 L/kg, and 0.30+/-0.13 L/h/kg, respectively. None of these pharmacokinetic parameters was found to be significantly different between the two groups.


CONCLUSIONS
The apparent lack of change in the relevant pharmacokinetic parameters of LTG during pregnancy may indicate that pregnancy has little or no effect on glucuronidation; the principal pathway for the drug's elimination.
Matar
K M
KM
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Nicholls
P J
PJ
Tekle
A
A
Bawazir
S A
SA
Al-Hassan
M I
MI
D000780:Anestrus / Q000097:blood / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D000077213:Lamotrigine; D049590:Postpartum Period / Q000097:blood / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000378:metabolism*; D014227:Triazines / Q000097:blood / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine