Clinical Pharmacology of the Angiotensin Receptor Antagonists

Domenic A. Sica, MD, Division of Clinical Pharmacology and Hypertension, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA.

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Volume of Distribution/Protein Binding

The AT1-RAs typically have a volume of distribution (VD) that approximates extracellular fluid volume, partly in relation to the extensive protein binding of these compounds. To date, the clinical significance of lower or higher VD of the AT1-RAs remains unclear. The VD of the AT1-RAs in disease states, such as renal failure, is unreported. Parenthetically, it has been suggested, though, that the greater the VD for an AT1-RA, the more likely it is that extravascular AT1 receptors can be accessed. The protein binding of the AT1-RAs is typically well in excess of 90%.[22,25,26,27,28,29,30] The exception to this pharmacologic characteristic is the AT1-RA irbesartan, which has the highest plasma free fraction (4%-5%). The extent of protein binding for the AT1-RAs remains fairly constant over a wide concentration range. The significance of the degree of protein binding remains to be determined.

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