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Endotoxin Induced Changes in the Pharmacokinetics of Warfarin in Rabbits
Endotoxin inducerede forandringer i warfarins farmakokinetik hos kaniner.
Acta Veterinaria Scandinavica volume 19, pages 479–486 (1978)
Abstract
The action of bacterial endotoxin on the pharmacokinetics of warfarin was investigated in rabbits injected with bacterial endotoxin from E. coli. High doses of endotoxin were able to change the kinetics of warfarin in rabbits by changing its volume of distribution. It is not possible to conclude whether the changes in elimination rate of warfarin in rabbits were mediated through changes in liver blood flow or through impairment of the metabolic capacity of the liver cells.
Sammendrag
Warfarins farmakokinetik blev undersøgt hos kaniner, der fik injektioner af endotoxin (E. coli). Store doser af endotoxin forårsagede chok, og hos kaniner med chok ændredes eliminationen og fordelingen af warfarin. En stor ændring i fordelingsvolumen medførte plasmakoncentrationer, der var højere end begyndelsesværdien. De foreliggende resultater tyder på, at der hos patienter med cirkulationsforstyrrelser induceret af endotoxin kan vrere risiko for toksiske plasmakoncentrationer eller overdosering af lægemidler efter gentagne doseringer.
References
Bachmann, K. & R. Shapiro: Protein binding of coumarin anticoagulants in disease states. Clin. Pharmacokin. 1977, 2, 110–126.
Benowitz, N. L. & W. Meister: Pharmacokinetics in patients with cardiac failure. Clin. Pharmacokin. 1976, 1, 389–405.
Brass, W.: Die Wirkung von Pyogenen bei Haustieren. (The effect of pyrogen in domestic animals). Proc. 17th Wld Vet. Congr. Hannover 1963, 165–169.
Elin, R. J., E. S. Vesell & S. M. Wolff: Effects of ethiocholanolone- induced fever on plasma antipyrine half-lives and metabolic clearance. Clin. Pharmacol. Ther. 1975, 178, 447–457.
Gorodischer, R., J. Krasner, J. J. McDevitt, J. P. Nolan & S. J. Yaffe: Hepatic microsomal drug metabolism after administration of endotoxin in rats. Riochem. Pharmacol. 1976, 25, 351–353.
Kato, R.: Drug metabolism under pathological and abnormal physiological states in animals and man. Xenobiotika 1977, 7, 25–92.
Ladefoged, O.: Absorptionen fra peritonealhulen. Eksperimentelle un- dersogelser over intraperitonealt applicerede laegemidlers far- makokinetik. (Absorption from the peritoneal cavity). Ph. D. Thesis, Copenhagen 1975, 79 pp.
Ladefoged, O.: Pharmacokinetics of trimethoprim (TMP) in normal and febrile rabbits. Acta pharmacol. (Kbh.) 1977, 41, 507–514.
Ladefoged, O.: The effect of E. coli endotoxin on the gastrointestinal absorption of antipyrine in rabbits. Proc. 13th Nord. Vet. Congr. Abo 1978, 363.
Ladefoged, O.: The pharmacokinetics of warfarin in hypoalbuminae- mic rabbits. To be published 1979.
Landy, M. & W. Braun: Bacterial Endotoxins. Quinn and Boden Go., New Jersey 1964.
van Miert, A. S. J. A. M. & J. Frens: The reaction of different animal species to bacterial pyrogens. Zbl. Vet.-Med. 1968, 15, 532–543.
Song, C. S., N. A. Gelb & S. M. Wolff: The influence of pyrogen-induced fever on salicylamide metabolism in man. J. clin. Invest. 1972, 51, 2959–2966.
Wolff, S. M. & J. V. Bennett: Editorial: Gram-negative-rod bacteriemia. New. Engl. J. Med. 1974, 291, 333–334.
Acknowledgment
The technical assistance of Mrs. Gerda Larsen is gratefully appreciated.
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Ladefoged, O. Endotoxin Induced Changes in the Pharmacokinetics of Warfarin in Rabbits. Acta Vet Scand 19, 479–486 (1978). https://doi.org/10.1186/BF03547587
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DOI: https://doi.org/10.1186/BF03547587