Apparent volumes of distribution and drug binding to plasma proteins and tissues

Summary A pharmacokinetic model that incorporates linear binding of drug to plasma proteins and tissue indicates the same relationship between apparent volume of distribution and drug binding as that proposed by Gillette (1971) based on a simple distribution model. Apparent volume of distribution (V) is directly proportional to free fraction of drug in plasma (f_p) and indirectly proportional to free fraction of drug in tissue (f_T). In the case of a constant f_T, a plot of V versus f_p will be linear with an intercept equal to plasma volume (V_p). If f_T changes with f_p, an apparently linear plot may result but the intercept will exceed V_p. An approach to the calculation of f_T, a composite binding parameter, is presented and illustrated by comparing the tissue binding of tolbutamide in patients during acute viral hepatitis and upon recovery.Supported in part by Grant GM-20852 from the National Institutes of Health.