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Multiple peaking phenomena in pharmacokinetic disposition
Neal M Davies1, Jody K Takemoto, Dion R Brocks
1Department of Pharmaceutical Sciences and Pharmacology and Toxicology Graduate Program, College of Pharmacy, Washington State University, Pullman, Washington 99164-6534, USA. ndavies@wsu.edu
Clinical Pharmacokinetics
|May 21, 2010
Summary
Multiple peaks in drug concentration-time curves can complicate pharmacokinetic analysis. This review explores formulation, gastrointestinal factors, and enterohepatic recycling as key causes of multiple peaking.
Area of Science:
- Pharmacokinetics
- Drug Metabolism
- Drug Formulation
Background:
- Multiple peaks in blood concentration-time profiles are observed in pharmacokinetics.
- This phenomenon poses challenges for determining and interpreting pharmacokinetic parameters.
Purpose of the Study:
- To review the various mechanisms contributing to multiple peaking in drug concentration-time curves.
- To discuss the implications of these mechanisms on pharmacokinetic parameter estimation.
Main Methods:
- Literature review of pharmacokinetic studies and drug formulation research.
- Analysis of physiological and biochemical factors influencing drug absorption and elimination.
- Discussion of specific examples illustrating different causes of multiple peaking.
Main Results:
- Multiple peaking can arise from drug formulation issues (e.g., excipients).
- Gastrointestinal tract physiology (pH, bile components) significantly impacts drug absorption.
- Enterohepatic recycling, involving biliary secretion and intestinal reabsorption, is a common cause of multiple peaks.
- Regional differences in the GI tract (e.g., transport proteins) can also contribute.
Conclusions:
- Understanding the causes of multiple peaking is crucial for accurate pharmacokinetic assessments.
- Formulation design and physiological interactions must be considered to mitigate or explain multiple peaking.
- Enterohepatic recycling requires special attention when calculating drug clearance and volume of distribution.
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