Title
Multiple peaking phenomena in pharmacokinetic disposition
Date Issued
27 May 2010
Access level
metadata only access
Resource Type
review
Author(s)
Washington State University
Abstract
Multiple peaking in the blood fluid concentration-time curve is a phenomenon occasionally encountered in pharmacokinetics. When it occurs, it can create difficulties in the determination and interpretation of pharmacokinetic parameters. Multiple peaking can occur as a consequence of a number of different mechanisms. These include, in addition to others, factors related to the formulation, be it the drug chemical entity itself or other formulation-related factors such as the excipients incorporated into the product design. Another contributing factor that can work in concert with the formulation is the physiological makeup of the gastrointestinal tract itself. This includes the pH and components of bile such as bile salts and phospholipids, the secretion of which is regulated by hormonal and dietary factors. In some cases, biochemical differences in the regional areas of the gastrointestinal tract, such as regiospecificity in bile concentrations andor transport proteins, could contribute to windows for absorption that result in multiple peaking of xenobiotics. One of the most common sources of multiple peaking is contributed by biliary secretion followed by intestinal reabsorption of a drug, a process for which the term 'enterohepatic recycling' has been coined. This cause of multiple peaking is associated with special consideration in the calculation and interpretation of the drug clearance and volume of distribution. In this review, each of these various causes of multiple peaking is discussed, with incorporation of relevant examples for illustrative purposes. © 2010 Adis Data Information BV. All rights reserved.
Start page
351
End page
377
Volume
49
Issue
6
Language
English
OCDE Knowledge area
Farmacología, Farmacia
Scopus EID
2-s2.0-77952567559
PubMed ID
Source
Clinical Pharmacokinetics
ISSN of the container
11791926
Sponsor(s)
This classification system identifies that the fundamental parameters governing the rate and extent of drug absorption are solubility and permeability. For instance, class I compounds are generally very well absorbed, often like an aqueous solution; however, gastric emptying can be the rate-limiting absorption step. Class II compounds exhibit dissolution-rate-limited absorption, and their bioavailability is very difficult to predict because of the large variability in the absorption and/or dissolution kinetics. Class III compounds exhibit permeability-rate-limited absorption. Class IV compounds tend to have very poor oral bioavailability.[146] This classification is widely recognized by regulatory agencies, including – but not limited to – the US FDA, the WHO, the European Medicines Agency, Health Canada, the Division of Drugs of the National Institutes of Health Services and the International Conference on Harmonization.
Sources of information:
Directorio de Producción Científica
Scopus