Blood coagulation-related parameter changes in Sprague-Dawley (SD) rats treated with phenobarbital (PB) and PB plus vitamin K.
Effects of dose and duration of phenobarbital (PB) administration and those of co-administration of PB and vitamin K on blood coagulation-related parameters were examined in specific pathogen-free (SPF) rats of Sprague-Dawley strain kept on an ordinary diet. In Experiment 1, oral administration of PB (0, 25, 50, 100 or 150 mg/kg/day) for 2 weeks induced increases in hepatic cytochrome P450 content and CYP2B expression, prolongation of coagulation time (activated partial thromboplastin time (APTT) and Thrombotest (TBT)) and an increase in anti-thrombin III (AT III) concentration in a dose-dependent manner. In Experiment 2, PB administration (100 mg/kg/day) for up to 14 days produced time-dependent increases in hepatic cytochrome P450 content and CYP2B (CYP2B1 and CYP2B2) expression. APTT was prolonged from day 1 and AT III concentration was increased from day 2, whereas the coagulation time (TBT) was prolonged from day 7. In Experiment 3, APTT prolonged by PB (100 mg/kg/day) was shortened after vitamin K(2) (30 mg/kg/day) co-administration, although AT III concentration was still increased. This suggests that not AT III but PB-induced vitamin K deficiency may play an important role in PB-induced prolongation of coagulation time in SPF rats kept on an ordinary diet.
Mochizuki
Masahiro
M
Toxicology Department, Gotemba Laboratory, Bozo Research Center Inc., Shizuoka. mochizuki@bozo.co.jp
Shimizu
Satomi
S
Kitazawa
Takahiro
T
Umeshita
Kazuhiko
K
Goto
Ken
K
Kamata
Takashi
T
Aoki
Ayumi
A
Hatayama
Kazuhisa
K
D000818:Animals; D000990:Antithrombin III / Q000032:analysis / Q000502:physiology; D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D010314:Partial Thromboplastin Time; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D014812:Vitamin K / Q000378:metabolism / Q000494:pharmacology*
D014812:Vitamin K; D000990:Antithrombin III; D010634:Phenobarbital