PubMed · 7807399
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A Rosen. 1994. Continuous quality improvement: principles and techniques.. https://pubmed.ncbi.nlm.nih.gov/7807399/
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BACKGROUND: Glucuronidation is a major drug-metabolizing reaction in humans. A pharmacological effect of glucuronide metabolites is frequently neglected and the value of therapeutic drug monitoring has been questioned. However, this may not always be true. METHODS: In this review the impact of glucuronidation on therapeutic drug monitoring has been evaluated on the basis of a literature search and experience from the own laboratory. RESULTS: The potential role of monitoring glucuronide metabolite concentrations to optimize therapeutic outcome is addressed on the basis of selected examples of drugs which are metabolized to biologically active/reactive glucuronides. Furthermore indirect effects of glucuronide metabolites on parent drug pharmacokinetics are presented. In addition, factors that may modulate the disposition of these metabolites (e.g. genetic polymorphisms, disease processes, age, and drug-drug interactions) are briefly mentioned and their relevance for the clinical situation is critically discussed. CONCLUSION: Glucuronide metabolites can have indirect as well as direct pharmacological or toxicological effects. Although convincing evidence to support the introduction of glucuronide monitoring into clinical practice is currently missing, measurement of glucuronide concentrations may be advantageous in specific situations. If the glucuronide metabolite has an indirect effect on the pharmacokinetics of the parent compound, monitoring of the parent drug may be considered. Furthermore pharmacogenetic approaches considering uridine diphosphate (UDP) glucuronosyltransferases polymorphisms may become useful in the future to optimize therapy with drugs subject to glucuronidation.
Major clinical advantages are achieved when direct thrombin inhibitors are used in venous thromboembolism. These agents provide more reliable anticoagulant response patterns because they are not significantly bound to plasma proteins and few, if any, drug-drug interactions are seen. The studies to date confirm that not all direct thrombin inhibitors are the same. The new reversible, short-acting catalytic site-specific drugs provide an excellent safety profile and high degree of efficacy for the prophylaxis and treatment of venous thromboembolism and pulmonary embolic states. The availability of the oral prodrug ximelagatran allows reproducible, effective, and safe direct thrombin inhibition without the requirement for coagulation laboratory monitoring; it appears destined to be the oral anticoagulant of the future.