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Free Drug Concentration Monitoring in Clinical Practice

Rationale and Current Status

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Summary

Recent advances in techniques to determine free drug concentrations have lead to a substantial increase in the monitoring of this parameter in clinical practice. The majority of drug binding to macromolecules in serum can be accounted for by association with albumin and α1-acid glycoprotein. Albumin is the primary binding protein for acidic drugs, while binding to α1-acid glycoprotein is more commonly observed with basic lipophilic agents. Alterations in the concentrations of either of these macromolecules can result in significant changes in free fraction. Diseases such as cirrhosis, nephrotic syndrome and malnourishment can result in hypoalbuminaemia. Burn injury, cancer, chronic pain syndrome, myocardial infarction, inflammatory diseases and trauma are all associated with elevations in the concentration of α1-acid glycoprotein. Treatment with a number of drugs has also been shown to increase α1-acid glycoprotein serum concentrations.

A wide variety of biological fluids have been examined for their ability to provide an estimation of free drug concentration at receptor sites. The most useful fluid for estimating free drug concentrations appears to be plasma or serum, with subsequent treatment of the sample to separate free and bound drug by an appropriate technique. The two most widely used methods are equilibrium dialysis and ultrafiltration. Of these two, ultraflltration has the greatest utility clinically because it is rapid and relatively simple. The major difficulty associated with this method involves the binding of drug to the ultrafilters, but significant progress has been made in solving this problem.

Several authors have enat]dorsed the routine use of free drug concentration monitoring. Data examining the clinical usefulness of free drug concentration monitoring for phenytoin, carbamazepine, valproic acid, disopyramide and lignocaine (lidocaine) are reviewed. While available evidence suggests that free concentrations may correlate with clinical effects better than total drug concentrations, there are insufficient data to justify the recommendation of the routine use of free drug concentration monitoring for any of these agents at present.

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  1. Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, Amherst, NY, 14260, USA

    Craig K. Svensson, Marlene N. Woodruff, James G. Baxter &  David Lalka

  2. Clinical Pharmacokinetics Laboratory, Buffalo General Hospital, Buffalo, USA

    Craig K. Svensson, Marlene N. Woodruff, James G. Baxter &  David Lalka

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Svensson, C.K., Woodruff, M.N., Baxter, J.G. et al. Free Drug Concentration Monitoring in Clinical Practice. Clin-Pharmacokinet 11, 450–469 (1986). https://doi.org/10.2165/00003088-198611060-00003

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