title: Phenobarbital (PB)-induced changes in blood coagulationrelated parameters in pregnant rats, lactating rats and pups.
abstract: Effects of repeated administration of phenobarbital (PB) on blood coagulation-related parameters were examined in non-pregnant, pregnant and lactating rats, and also in pups born to PB-treated lactating dams. PB was orally administered at a dose level of 80 mg/kg/day to pregnant (from gestation day (GD) 13), postpartum (from postpartum day (PPD) 7) and non-pregnant rats (from 13 weeks of age) for 7 days. Blood was collected on GD20 or PPD14 to perform blood coagulation examination. Concurrently, the blood coagulation parameters were examined in the pups. Increases in liver weight and/or hepatic cytochrome P450 content were observed in the PB-treated non-pregnant, pregnant and lactating rats. Activated partial thromboplastin time (APTT) was prolonged and anti-thrombin III (ATIII) concentration was increased in the lactating rats, while there were no changes in prothrombin time (PT) or APTT in the non-pregnant and pregnant rats. Moreover, prolongation of PT and APTT and decreases in factors VII and IX activities were observed in their pups. Thus, prolongation of blood coagulation time was confirmed in both dams and their pups following PB-administration to lactating dams. Effects of vitamin K(2) (VK(2)) on PB-induced changes in blood coagulation-related parameters of both dams and their pups were examined by co-administration with PB and VK(2) to lactating dams. PT and APTT were comparable to the control and PB-induced prolongation of blood coagulation time was improved in the pups while APTT was prolonged in dams, suggesting that VK(2) was beneficial to pups but not to dams.
authors: Bozo Research Center Inc. Shizuoka, Japan. mochizuki@bozo.co.jp
authors: Masahiro
authors: M
authors: Mochizuki
authors: Satomi
authors: S
authors: Shimizu
authors: Yuri
authors: Y
authors: Kidokoro
authors: Takashi
authors: T
authors: Kamata
authors: Takahiro
authors: T
authors: Kitazawa
authors: Daisuke
authors: D
authors: Kishi
authors: Emi
authors: E
authors: Okazaki
authors: Yoshito
authors: Y
authors: Nishihata
authors: Takumi
authors: T
authors: Ohishi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D007774:Lactation / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000008:administration & dosage / Q000009:adverse effects*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D024482:Vitamin K 2 / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D001779:Blood Coagulation Factors; D024482:Vitamin K 2; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital