[Influence of indometacin farnesil on blood coagulation. Comparison with indomethacin in normal rats and warfarin induced hypoprothrombinemic rats].
The influence of indometacin farnesil (IMF), a prodrug of indomethacin, on blood coagulation was compared with indomethacin (Ind) in normal rats and warfarin treated rats. In normal rats, 30 mg/kg of Ind very markedly shortened the extrinsic coagulation time and decreased the hematocrit, GOT, GPT and ALP in plasma at 24 hr after administration, but 3 mg/kg of Ind and both 10 and 100 mg/kg of IMF did not influence any parameter. In warfarin treated rats, 2.5 mg/kg of Ind decreased the normal prothrombin level at 48 hr, and 10 mg/kg of Ind prolonged the blood coagulation time, decreased the normal prothrombin level and hematocrit, and increased the PIVKA-II level. Moreover, at 48 hr, 3 of 6 rats in the 10 mg/kg Ind-administered group died due to intestinal bleeding. IMF at all dosages examined did not affect any of the above parameters.
Hara
K
K
Department of Pharmacology, Tokyo Research Laboratories, Eisai Co., Ltd., Japan.
Akiyama
Y
Y
Kato
Y
Y
Orikasa
E
E
Takahira
H
H
Tajima
T
T
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers; D001777:Blood Coagulation / Q000187:drug effects*; D004347:Drug Interactions; D006400:Hematocrit; D007020:Hypoprothrombinemias / Q000097:blood*; D007213:Indomethacin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D011498:Protein Precursors / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014859:Warfarin / Q000494:pharmacology*
D015415:Biomarkers; D011498:Protein Precursors; C008208:acarboxyprothrombin; D014859:Warfarin; D011516:Prothrombin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; C060022:indomethacin farnesil; D007213:Indomethacin