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Phenobarbital (PB)-induced changes in blood coagulationrelated parameters in pregnant rats, lactating rats and pups

Masahiro Mochizuki1, Satomi Shimizu, Yuri Kidokoro

  • 1Bozo Research Center Inc. Shizuoka, Japan. mochizuki@bozo.co.jp

The Journal of Toxicological Sciences
|December 3, 2009
PubMed

Insights

Phenobarbital (PB) administration prolonged blood clotting times in lactating rats and their pups. Vitamin K2 (VK2) improved clotting in pups but not dams, indicating differential effects.

Area of Science:

  • Pharmacology
  • Toxicology
  • Biochemistry

Background:

  • Phenobarbital (PB) is known to affect liver enzymes and drug metabolism.
  • The impact of PB on blood coagulation, particularly during pregnancy and lactation, requires further investigation.
  • Understanding these effects is crucial for assessing risks in vulnerable populations.

Purpose of the Study:

  • To investigate the effects of repeated phenobarbital (PB) administration on blood coagulation parameters in non-pregnant, pregnant, and lactating rats.
  • To evaluate the impact of PB exposure on coagulation in pups born to treated dams.
  • To assess the efficacy of vitamin K2 (VK2) in mitigating PB-induced coagulation changes.

Main Methods:

  • Rats (non-pregnant, pregnant, lactating) received daily oral doses of PB (80 mg/kg) for 7 days.
  • Blood samples were collected for coagulation tests (PT, APTT) and anti-thrombin III (ATIII) concentration.
  • Coagulation parameters were also assessed in pups born to PB-treated lactating dams.
  • Co-administration of PB and VK2 was used to evaluate VK2's protective effects.

Main Results:

  • PB increased liver weight and hepatic cytochrome P450 content in treated rats.
  • Lactating rats showed prolonged activated partial thromboplastin time (APTT) and increased anti-thrombin III (ATIII) concentration.
  • Pups exhibited prolonged prothrombin time (PT) and APTT, with decreased factors VII and IX activities.
  • Vitamin K2 (VK2) improved PB-induced coagulation prolongation in pups but not in dams.

Conclusions:

  • Repeated PB administration significantly alters blood coagulation in lactating rats and their offspring.
  • PB exposure during lactation poses a risk for coagulation disturbances in both dams and pups.
  • Vitamin K2 (VK2) shows potential therapeutic benefit for PB-induced coagulopathy in pups, but not in dams.

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