Pharmacokinetic behavior presents drug therapy challenges
1Eugene Applebaum College of Pharmacy & Health Sciences, Wayne State University, 259 Mack Ave, Detroit, MI 48201, USA +313 577 1574 rls@wayne.edu.
Expert Review of Clinical Pharmacology
|October 30, 2013
Summary
Managing drug therapy is challenging when conditions significantly alter drug clearance. This review covers recent findings on how critical illness, genetic variations, and drug interactions impact drug clearance, affecting patient response and toxicity.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Genetics
Background:
- Drug clearance is crucial for optimizing therapeutic efficacy and minimizing toxicity.
- Significant alterations in drug clearance can complicate drug management.
- Recent literature highlights pathophysiologic, genetic, and drug interaction factors influencing drug clearance.
Purpose of the Study:
- To review recent literature (past 5 years) on conditions affecting drug clearance.
- To evaluate how pathophysiologic and genetic factors alter drug clearance.
- To examine drug interactions that significantly change drug clearance.
Main Methods:
- Literature review focusing on studies published within the last five years.
- Analysis of conditions leading to increased drug clearance.
- Analysis of conditions leading to decreased drug clearance.
Main Results:
- Increased drug clearance observed in augmented renal clearance (critically ill patients), ultrafast metabolism (gene duplication), and rifampin-induced enzyme induction.
- Decreased drug clearance noted in multiple organ failure, non-functioning CYP2D6 and CYP2C8/9 alleles, and CYP3A4 interactions (erythromycin, clarithromycin).
- Evaluated conditions alter drug clearance to a degree that challenges therapeutic management.
Conclusions:
- Pathophysiologic states, genetic polymorphisms, and drug interactions substantially impact drug clearance.
- Altered drug clearance necessitates careful drug management to optimize outcomes.
- Understanding these changes is vital for personalized pharmacotherapy.
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