Regional pharmacokinetics. I. Physiological and physicochemical basis.

Systemic pharmacokinetics is the study of the time-course of drug concentrations in 'systemic' blood sampled from either an arterial, central venous or peripheral venous blood vessel. It is generally not suitable for studying the pharmacokinetics of drugs in individual organs of the body, when the blood concentrations of a drug are changing rapidly, or when the physiological or pathophysiological status of a patient is unstable. Regional pharmacokinetics addresses some of these limitations and is based on the study of the factors influencing drug concentrations in specific regions (tissues, organs) of the body due to the movement of drug from blood into and out of the region (drug 'uptake' and 'elution', respectively). It provides a vital link between systemic pharmacokinetics and molecular pharmacology. The physiological basis of regional pharmacokinetics is a function of the interactions of the drug between the cells and proteins in blood, the blood flow supplying a region, the structure of the capillaries of the region and the types of specific and non-specific binding within the region. The physicochemical basis of regional pharmacokinetics is a function of the factors influencing the rate and extent of diffusion of a drug through aqueous and lipid mediums, such as molecular weight, ionization, charge, and lipophilicity.