Relationships between opioid disposition and their pharmacological effects--an overview

The understanding of the metabolic disposition and pharmacokinetics of opioid analgesics and their relationship to therapeutic and adverse effects has been an area of considerable research activity in the past two decades and has provided the beginning of an applied science in this area. Given the experimental nature and complexity of pharmacokinetic/pharmacodynamic relationships and the state of the art in this area, the most meaningful therapeutic conclusions and extrapolations remain those based on the results of the most adequate and well-controlled therapeutic evaluations. In contrast, advances in analytical methodology and an understanding of the pharmacokinetics of opioid analgesics in specific patient populations (e.g. severe hepatic cirrhosis, renal failure) have provided clinically useful guidance towards the appropriate precautions for the use of opioid analgesics.