Abstract
Liver function alterations, in the adjuvant induced polyarthritis procedure in rats, has been demonstrated by many investigators. We observed a significant inhibition of the polyarthritis with phenylbutazone but we were unable to find any changes in the relative liver weights or SGPT, AP or BUN in polyarthritic or phenylbutazone treated rats. However, we did observe that polyarthritic rats maintained a significantly higher plasma phenylbutazone concentration than the corresponding non-arthritic controls. This appears to futher substantiate the influence of ‘pathopharmacodynamics’ on the disposition and activity of drugs.
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References
C. M. Pearson, B. Waksman andT. Sharp,Studies of Arthritis and other Lesions Induced in Rats by Injections of Mycobacterium Adjuvant, J. Exp. Med.113, 485 (1961).
C. M. Pearson andF. D. Wood,Studies of Arthritis and other Lesions Induced in Rats by the Injection of Mycobacterium Adjuvant, Am. J. Path.42, 73 (1963).
B. B. Neubould,Chemotherapy of Arthritis Induced in Rats by Mycobacterium Adjuvant, Br. J. Pharmac.21, 127–136 (1963).
E. M. Glenn andJ. Gray,Adjuvant-Induced Polyarthritis in Rats: Biologic and Histologic Background, Am. J. Vet. Res.26, 1180–1194 (1965).
S. J. Piliero, M. L. Graeme, E. B. Sigg, G. Chinea andC. Colombo,Action of Anti-Inflammatory Agents Upon Blood and Histophathologic Changes Induced by Periarthritis in Rats, Life Sci.5, 1057–1069 (1966).
C. Reinicke andW. Klinger,Effects of Non-Stero. dal Anti-Rheumatic Agents on Microsomal Drui-Metabolizing Enzymes of Rat Liver, Biochem. Pharg mac.20, 1405–1412 (1971).
L. F. Prescott,Clinically Important Interactions, Drugs5, 161–186 (1973).
A. Mills,Non-Steroidal Anti-Inflammatory Drugs, New Engl. J. Med.290, 781 (1974).
A. K. Cho, B. J. Hodshon andB. B. Brodie,Effects of Phenylbutazone on Liver Microsomal Demethylase, Biochem. Pharmac.19, 1817–1823 (1970).
R. A. O'Reilly,The Binding of Sodium Warfarin to Plasma Albumin and its Displacement by Phenylbutazone, Ann. N.Y. Acad. Sci.226, 293–308 (1973).
E. Jöhnchen andG. Levy,Inhibition of Phenylbutazone Elimination by its Metabolite Oxyphenbutazone, Proc. Soc. exp. Biol. Med.141, 963–965 (1972).
M. D. Chaplin, A. P. Roszkowski andR. K. Richards,Displacement of Thiopental from Plasma Proteins by Non-Steroidal Anti-Inflammatory Agents, Proc. Soc. exp. Biol. Med.143, 667–671 (1973).
J. J. Burns, R. K. Rose, T. Chenken, A. Goldman, A. Schulert andB. B. Brodie,The Physiological Disposition of Phenylbutazone (Butazolidin) in Man and a Method of its Estimation in Biological Material J. Pharm. exp. Ther.109, 346 (1953).
P. G. Dayton, I. H. Zafar andM. Perel,Influence of Binding on Drug Metabolism and Distribution, Ann. N.Y. Acad. Sci.226, 172 (1973)
E. M. Glenn, J. Gray andW. Kooyers,Chemical Changes in Adjuvant-Induced Polyarthritis of Rats, Am. J. Vet. Res.26, 1195–1203 (1965).
A. Quevauviller, M. A. Chalchat, H. Brouilhet andF. Delbarre,Actions des Barbituriques chez le rat atteint d'une polyarthrite à adjuvant, C. r. Soc. Biol.162, 618–619 (1968).
D. M. Morton andD. H. Chatfield,The Effects of Adjuvant-Induced Arthritis on the Liver Metabolism of Drugs in Rats, Biochem. Pharmac.19, 473–481 (1970).
B. Sylvia Zak, F. Honc andG. Lukas,Reversal of Impaired Hepatic Functions in the Adjuvant Arthritic Rat by Anti-Inflammatory Drugs, 5th Int. Congr. Pharmac., p. 259 (abst.) (1972).
M. W. Whitehouse andF. J. Beck,Impaired Drug Metabolism in Rats with Adjuvant-Induced Arthritis: A Brief Review, Drug Metab. Disp.1, 251 (1973).
F. J. Beck andM. W., Whitehouse,Effect of Adjuvant Disease in Rats on Cyclophosphamide and Isophosphamide Metabolism, Biochem. Pharmac.22, 2453–2468 (1973).
G. DiPasquale, P. Welaj andC. Rassaert,Prolonged Pentobarbital Sleeping Time in Adjuvant-Induced Polyarthritic Rats (in press).
G. DiPasquale andP. Welaj,Ulcerogenic Potential of Indomethacin in Arthritic and Non-Arthritic Rats, J. Pharm. Pharmac.25, 831–832 (1973).
W. H. March, B. Fingerhut andE. Kirsch,Adaption of an Alkaline Phosphatase Method for Automatic Colorimetric Analysis, Clin. Chem.5, 119 (1959).
W. H. March, B. Fingerhut andE. Kirsch,Determination of Urea Nitrogen with the Diacetyl Method and an Automatic Dialyzing Apparatus, Am. J. Clin. Path.28, 681–688 (1957).
Technicon Auto Analyzer Fluorometric Method N-54P.
D. S. Platt andB. L. Cockrill,Biochemical Changes in Rat Liver in Response to Treatment with Drugs and Other Agents. I. Effects of Anti-Convulsant, Anti-Inflammatory, Hypocholesterolemic and Adrenergic β-Blocking Agents, Biochem. Pharmac.18, 429 (1969).
E. Schwartz, J. Tornaben andG. Boxill,The Effects of Food Restriction on Hematology, Clinical Chemistry and Pathology in Albino Rats, Toxic. appl. Pharmac.25, 515 (1973).
A. D. Poland, D. Smith, R. Kuntzman, M. Jacobson andA. H. Conney,Effect of Intensive Occupational Exposure to DDT on Phenylbutazone and Cortisol Metabolism in Human Subjects, Clin. Pharmac. Ther.11, 724 (1970).
I. L. Sperling,Untoward Effects of Phenylbutazone. A Re-evaluation, Arth. Rheum.2, 203 (1959).
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DiPasquale, G., Rassaert, C., Welaj, P. et al. Effect of single and multiple treatments with phenylbutazone in normal and adjuvant-induced polyarthritic rats. Agents and Actions 5, 52–56 (1975). https://doi.org/10.1007/BF02027159
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DOI: https://doi.org/10.1007/BF02027159