PHARMACOLOGICAL RESPONSE KINETICS OF CHLORPROMAZINE IN RABBITS
Abstract
Control systems analysis techniques are implemented to accomplish the principle objective of pharmacokinetic research: the development of mathematical model descriptions of the dynamics of drug transference and drug effects in pharmacologically responding systems. A theoretical basis is developed for the performance of a pharmacokinetic analysis of drug action utilizing data obtained from the observation of the time course of pharmacological response intensities following dosing of a drug by any route of administration. It is demonstrated that through the suitable use of intravenous dose-effect curves, the postulation of hypothetical models for drug-receptor interaction is obviated. The dose-effect curve graphically provides the relationship between the quantity of drug at the biophase and the observed intensity of drug response. The present study involves the use of the drug chlorpromazine to induce certain pharmacological responses in rabbits that can be quantitated and transformed into relative biophasic drug levels via dose-effect curves. This data provides the input to computational procedures that yield mathematical model descriptions of the biokinetic behavior of the drug in this system. The pharmacological responses investigated in this study include: drug induced rectal temperature depression, pupillary diameter decrease, intraocular pressure decrease, and changes in the electroencephalogram and electrocardiogram. Mathematical models that are reflective of the dynamics of chlorpromazine activity in rabbits were determined and verified for drug induced rectal temperature depression, pupillary diameter decrease, and intraocular pressure decrease. The nature of drug induced changes in the electroencephalogram and electrocardiogram were such that adequate model representations could not be obtained, as no clearly graded intensity of pharmacological response could be observed using data from these two responses.
Degree
Ph.D.
Subject Area
Pharmacology
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.