Impact of pregnancy on zonisamide pharmacokinetics in rabbits.
Pregnancy is associated with various physiological changes which may lead to significant alterations in the pharmacokinetics of many drugs. The present study was aimed to investigate the potential effects of pregnancy on the pharmacokinetic profile of zonisamide (ZNM) in the rabbit. Seven female rabbits were used in this study. The pregnant and nonpregnant rabbits received ZNM orally at a dose of 10 mg/kg and blood samples were collected from the animals just before receiving the drug and then serially for up to 24 h. The plasma samples were analyzed using tandem mass spectrometric method. Following a single oral dose of ZNM to the rabbits, the mean values of ZNM plasma concentrations at different times were consistently low in pregnant compared to nonpregnant rabbits. The mean values of ZNM's Cmax and AUC0-∞ were significantly (P < 0.05) decreased, whereas the CL/F exhibited substantial increase (P < 0.05) in pregnant compared to nonpregnant rabbits. Tmax, t1/2abs, t1/2el, MRT, and Vd/F showed no significant differences between the two groups. The present study demonstrates that pregnancy decreased ZNM plasma concentrations in rabbits and that the decrease could be due to decreased extent of gastrointestinal absorption, induced hepatic metabolism, or enhanced renal elimination of the drug.
Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, 13110 Safat, Kuwait.
Kamal M
KM
Matar
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011247:Pregnancy; D011817:Rabbits; D053719:Tandem Mass Spectrometry; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide