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ABSENCE OF CHANGES IN DRUG DISPOSITION AND CATECHOLAMINE SENSITIVITY IN THE HYPERTHYROID DOG
Author(s) -
ISHIZAKI TAKASHI,
TAWARA KAZUJI
Publication year - 1980
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1980.tb10919.x
Subject(s) - euthyroid , chronotropic , propranolol , endocrinology , medicine , catecholamine , isoprenaline , chemistry , volume of distribution , thyroid , heart rate , pharmacokinetics , blood pressure , stimulation
1 In order to study the relative contribution of hepatic drug metabolizing enzymes and hepatic blood flow to the clearance of drugs in the hyperthyroid state, the disposition kinetics of two model compounds (antipyrine and propranolol) were examined in thyroid‐fed dogs as compared to euthyroid and phenobarbitone‐pretreated animals. 2 In hyperthyroid dogs, the possibility of catecholamine hypersensitivity was evaluated by assessing the chronotropic response to isoprenaline and by constructing a drug concentration‐effect (β‐blockade) relationship. 3 The plasma propranolol half‐life (0.97 ± 0.12 h) of the hyperthyroid animals did not differ significantly from either the euthyroid group or the phenobarbitone‐pretreated group. This was observed with no significant change in the apparent volume of distribution among the three experimental groups. 4 Phenobarbitone pretreatment accelerated significantly the elimination of antipyrine (half‐life, 1.09 ± 0.15 h, P < 0.01) as compared to the euthyroid (2.84 ± 0.35 h) and the hyperthyroid groups (2.58 ± 0.13 h), respectively, without any changes in the apparent volume of distribution in any group. 5 Neither the chronotropic responses to exogenously administered catecholamine, nor the antagonist concentration‐effect relationships support the concept that the hyperthyroid state potentiates sensitivity of the receptor‐effect system of the heart. 6 The data obtained from the present study fit best with the view that thyroid hormone excess alters neither the disposition of the model compounds used nor the catecholamine‐sensitivity examined.