In general, drug companies avoid development of drugs that exhibit non-linear kinetics. Give your opinion on why this may be the case.
Answers
Previous chapters discussed linear pharmacokinetic models using simple first-order kinetics to describe the course of drug disposition and action. These linear models assumed that the pharmacokinetic parameters for a drug would not change when different doses or multiple doses of a drug were given. With some drugs, increased doses or chronic medication can cause deviations from the linear pharmacokinetic profile previously observed with single low doses of the same drug. This nonlinear pharmacokinetic behavior is also termed dose-dependentpharmacokinetics.
Many of the processes of drug absorption, distribution, biotransformation, and excretion involve enzymes or carrier-mediated systems. For some drugs given at therapeutic levels, one of these specialized processes may become saturated. As shown in Table 9-1, various causes of nonlinear pharmacokinetic behavior are theoretically possible. Besides saturation of plasma protein-binding or carrier-mediated systems, drugs may demonstrate nonlinear pharmacokinetics due to a pathologic alteration in drug absorption, distribution, and elimination. For example, aminoglycosides may cause renal nephrotoxicity, thereby altering renal drug excretion. In addition, gallstone obstruction of the bile duct will alter biliary drug excretion. In most cases, the main pharmacokinetic outcome is a change in the apparent elimination rate constant.