Abstract
A time-dependent volume shift from buffer to plasma, which occurs during equilibrium dialysis, decreased the protein binding of disopyramide and its capacity constant, and had no effect on the binding association constant. The volume-dependent decrease in disopyramidine binding may be corrected for by use of a derived equation. Inclusion of dextran, 2.5% (w/v), and use of a thick, low molecular weight cutoff membrane was the most effective technique in attenuating the volume shift. The plasma (serum) protein binding of the basic drugs lidocaine, disopyramide,propranolol, and diazepam was decreased when protein was diluted to 88 % or less of its undiluted concentration as a consequence of the volume shift. The protein binding of clofibrate, a highly bound acid drug, was more sensitive to volume shifts than the four basic drugs. Correction of drug binding for volume shifts was reasonably successful for most drugs. The highest binding measured for all drugs was associated with the lowest volume shift.
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This work was supported by Grant GM-28424 from the National Institute of General Medical Sciences, National Institutes of Health, and by a grant from the Central Ohio Heart Association. Dr. MacKichan is the recipient of a Young Investigatorship from The American Heart Association, Central Ohio Chapter.
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Lima, J.J., MacKichan, J.J., Libertin, N. et al. Influence of volume shifts on drug binding during equilibrium dialysis: Correction and attenuation. Journal of Pharmacokinetics and Biopharmaceutics 11, 483–498 (1983). https://doi.org/10.1007/BF01062207
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DOI: https://doi.org/10.1007/BF01062207