CHAPTER ONE
INTRODUCTION
1.1 Pharmacokinetics
Pharmacokinetics is the study of the time course of drug and metabolite levels in different fluids, tissues, and excreta of the body, and of the mathematical relationships required to develop models to interpret such data (Gibaldi and Perrier, 2004). Neligan (2006) defined Pharmacokinetics as the study of what the body does to a drug.
Pharmacokinetics can also be defined as the study of the time course of drug movement in the body during absorption, distribution, metabolism and elimination (excretion and biotransformation) (Sadee and Beelen, 1980; Coker, 2001). Pharmacokinetic studies can be applied for the safe and effective therapeutic management of a patient. The pharmacokinetic profile of a drug strongly influences its delivery to biological targets, thereby affecting its efficacy and potential side effects (Van de water beemd and Gifford, 2003).
The Pharmacokinetics of a compound are typically understood, analyzed and interpreted in the context of their underlying absorption, distribution, metabolism and excretion (ADME) processes (Gram, 2003). However, there is no unique mathematical model for any of these processes, usually a number of different models with different underlying assumptions, parameterization and applicability are concurrent (Poulin and Theil, 2002). Absorption is the process by which a drug proceeds from the site of administration to the site of measurement within the body (Brodie, 2007).
The routes of drug administration are: oral, intravenous, buccal, sublingual, rectal, intramuscular, transdermal, subcutaneous, inhalational and topical (Neligan, 2006). Of all these routes, the usual way of administration is the oral route (Benet, 1998). The rate of absorption of a drug depends upon its dissolution characteristics, its ability to pass through biological membranes and upon a number of physiological variables (gastrointestinal) motility, presence of food in gastrointestinal tract etc. Apart from physiochemical properties of the drug (ionization constant, lipid-en water solubility, molecular radius, diffusion coefficient) also the pharmaceutical formulation may be of extreme importance in determining rate of absorption (Bozler and Van Rossum, 2002). We have linear and non-linear absorptions. Linear absorption is the type of absorption whereby the free diffusion of a drug through biomembranes is the rate limiting step in absorption. The non-linear absorption is the type of absorption where some other steps become the rate limiting step.
For instance, dissolution of drug in the gastrointestinal fluid, non-linear phenomenon in the absorption process will arise (Birkett, 2002). Some drugs require the presence of food in the gastrointestinal tract to be absorbed, others on the contrary are better absorbed when taken in an empty stomach (Health Encyclopedia, 2006). Distribution is the process of reversible transfer of a drug to and from the site of measurement (Birkett, 2002). Some of the factors that determine the distribution of a drug in the body are: blood flow; protein binding; and lipid solubility and the degree of ionization.
THE EFFECTS OF CHLOROQUINE, PARACETAMOL AND PROMETHAZINE ON THE PHARMACOKINETICS OF CHLORPROPAMIDE IN HUMAN VOLUNTEERS
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