Kinetics of drug action in disease states. XXXIV. Effect of experimental thyroid disorders on the pharmacodynamics of phenobarbital, ethanol and pentylenetetrazol.
To determine the effect of thyroid disorders on the concentration-activity relationship of certain drugs acting on the central nervous system, rats were made hyperthyroid by administration of L-thyroxine and hypothyroid by administration of propylthiouracil. They then received a slow i.v. infusion of phenobarbital or ethanol until they lost their righting reflex, or of pentylenetetrazol until the onset of maximal seizures. Drug concentrations in serum, brain and cerebrospinal fluid (CSF) were determined at these pharmacologic endpoints. Hyperthyroidism was associated with a statistically significant increase in the infused hypnotic dose and brain concentration of phenobarbital but had no apparent effect on concentrations of the drug in serum and CSF. The hypnotic dose of ethanol was increased significantly in hyperthyroid rats and decreased in hypothyroid animals; ethanol concentrations in serum, brain and CSF at onset of effect were generally not affected by thyroid dysfunction except for a small but statistically significant increase of serum ethanol concentrations in the hyperthyroid rats. The convulsant dose of pentylenetetrazol was reduced significantly in hypothyroid animals and unaltered in hyperthyroid rats; the concentrations of the convulsant in serum, brain and CSF were not apparently changed by the thyroid dysfunctions. In general, experimental thyroid disorders had no pronounced effect on the pharmacodynamics (concentration-effect relationship) of phenobarbital, ethanol and pentylenetetrazol in rats.
Walker
J S
JS
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo, Amherst.
Levy
G
G
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics*; D005260:Female; D010433:Pentylenetetrazole / Q000493:pharmacokinetics*; D010634:Phenobarbital / Q000493:pharmacokinetics*; D051381:Rats; D011917:Rats, Inbred Lew; D013959:Thyroid Diseases / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood / Q000493:pharmacokinetics
D000431:Ethanol; D013974:Thyroxine; D010433:Pentylenetetrazole; D010634:Phenobarbital