Pharmacokinetics of drugs in overdose.

The pharmacokinetics of drugs may be altered following an overdose. The degree of absorption depends on the physical characteristics of the drug; the rate of dissolution may delay or broaden peak serum concentrations. The pathophysiological effects of a drug may also limit or augment absorption. Altered distribution of drugs in overdose results from changes in the extent of protein binding and size of the volume of distribution. Saturation of hepatic enzyme systems in overdose is manifested by delayed metabolism or elimination of many drugs; renal elimination of unchanged drug may take on greater importance in this instance. Familiarity with the toxicokinetic profile of a given drug enables the physician to exploit these principles in order to limit toxicity. Delayed or prolonged absorption allows for late decontamination. Multiple doses of activated charcoal are effective in interrupting both entero-enteric and enterohepatic recirculation. Alkalinisation-induced ion trapping enhances renal elimination of unchanged drugs which normally undergo hepatic transformation. For several drugs, chronic overdose due to altered distribution is associated with a greater severity of toxic manifestations despite relatively low serum drug concentrations. Conversely, with some drugs, induction of metabolic pathways may lead to more rapid drug elimination in chronic overdose. Knowledge of the pharmacokinetic alterations which occur in drug overdose enables the physician to predict toxicity with greater accuracy and to institute optimum therapy in a timely manner.