Influence of febrile disease on the pharmacokinetics of veterinary drugs.
In mammals, tissue damage, inflammation or invasion of pathogenic microorganisms induces systemic changes, collectively known as the 'acute phase response'. Among the varied alterations, which together produce this response, are: fever, inappetence, inhibition of gastric function, synthesis of hepatic acute phase proteins and changes in blood flow to various organs. The intensity of these different reactions may vary depending upon the type of invading microorganism or bacterial toxin given. Considerable attention has been paid to the involvement of pyrogenic cytokines derived from reticuloendothelial cells and phagocytes in the host responses to infection. These cytokines include interleukins, interferons and tumor necrosis factor. In the present paper, attention has been focused on the role of cytokines and the effects of the acute phase response on drug disposition in disease states (including the effect of anorexia on medicated feed intake and drug bioavailability). From the disease-induced changes in pharmacokinetics, it follows that more attention should be paid to drug disposition in patients in relation to efficacy, side effects and drug residues in food products. In relation to good veterinary practice, it is also recommended that the route of administration, dosage and withdrawal time be adjusted according to the severity of the disease.
van Miert
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Department of Veterinary Basic Sciences, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
D000210:Acute-Phase Reaction / Q000378:metabolism*; D000818:Animals; D001066:Appetite / Q000502:physiology; D001682:Biological Availability; D001711:Biotransformation; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000502:physiology; D005334:Fever / Q000378:metabolism*; D008322:Mammals; D010599:Pharmacokinetics; D014018:Tissue Distribution