ABSTRACT
If a drug is administered intravenously via a constant-rate pump, and blood sampled from a distant vein for measurement of drug concentration, a plot of plasma concentration versus time can be constructed (Figure 3.1). The concentration rises from zero, rapidly at first and then more slowly until a plateau (representing steady state) is approached. At steady state, the rate of input of drug to the body equals the rate of elimination. The concentration at plateau is the steady-state concentration (CSS). This depends on the rate of drug infusion and on its ‘clearance’. The clearance is defined as the volume of fluid (usually plasma) from which the drug is totally eliminated (i.e. ‘cleared’) per unit time. At steady state,
administration rate elimination rate
elimination rate CSS clearance
so
clearance administration rate/CSS
● ● Constant-rate infusion 11 ● Single-bolus dose 12 ● Repeated (multiple) dosing 13
● Deviations from the one-compartment model with first-order elimination 14
● Non-linear (‘dose-dependent’) pharmacokinetics 15
Pharmacokinetics is the study of drug absorption, distribution, metabolism and excretion (ADME) – ‘what the body does to the drug’. Understanding pharmacokinetic principles, combined with specific information regarding an individual drug and patient, underlies the individualized optimal use of the drug (e.g. choice of drug, route of administration, dose and dosing interval).
