Introduction

Pharmacokinetics can be defined as the study of drug and drug metabolite concentrations within the body. It describes how drug concentrations may vary over time owing to the different phases after drug administration, namely absorption, distribution, metabolism and elimination. Knowledge of changes in critical illness and after major surgery may allow prediction of the correct dose and regime to ensure therapeutically effective levels at the site of action. In critical care, the pathophysiological changes over the course of the illness may significantly alter the pharmacokinetic behaviour of drugs. Therefore, changes may need to be made at different times to prevent over- or underdosing.

Pathophysiology

To understand the correct principles of drug administration in critical illness, it is necessary to identify which pathophysiological changes at what point during critical illness.

Gastrointestinal absorption

Drug absorption in the gastrointestinal tract after oral administration is a kinetic process, which may be reduced by an unpredictable amount in the early postoperative period after major surgery. It is reduced due to gastric stasis, metabolic imbalance or reduced splanchnic blood flow associated with hypotension and use of inotropic agents. Therefore, the intravenous route may be preferable until enteral/oral feeding is established, to ensure therapeutic levels are achieved.