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Cheng H, Gillespie WR. Volumes of distribution and mean residence time of drugs with linear tissue distribution and binding and nonlinear protein binding. J Pharmacokinet Biopharm. 1996;24(4):389-402doi: 10.1007/BF02353519.
Cheng, H., & Gillespie, W. R. (1996). Volumes of distribution and mean residence time of drugs with linear tissue distribution and binding and nonlinear protein binding. Journal of pharmacokinetics and biopharmaceutics, 24(4), 389-402. https://doi.org/10.1007/BF02353519
Cheng, H, and Gillespie, W R. "Volumes of distribution and mean residence time of drugs with linear tissue distribution and binding and nonlinear protein binding." Journal of pharmacokinetics and biopharmaceutics vol. 24,4 (1996): 389-402. doi: https://doi.org/10.1007/BF02353519
Cheng H, Gillespie WR. Volumes of distribution and mean residence time of drugs with linear tissue distribution and binding and nonlinear protein binding. J Pharmacokinet Biopharm. 1996 Aug;24(4):389-402. doi: 10.1007/BF02353519. PMID: 9044167.
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J Pharmacokinet Biopharm. 1996 Aug;24(4):389-402. doi: 10.1007/BF02353519.

Volumes of distribution and mean residence time of drugs with linear tissue distribution and binding and nonlinear protein binding.

Journal of pharmacokinetics and biopharmaceutics

H Cheng, W R Gillespie

Affiliations

  1. Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.

PMID: 9044167 DOI: 10.1007/BF02353519

Abstract

Based on a generalized model, equations for calculating the mean residence time in the body at single dose (MRT) and at steady state (MRTss), apparent steady-state volume of distribution (Vss), and steady-state volume of distribution (Vss) are derived for a drug exhibiting nonlinear protein binding. Interrelationships between Vss and Vss as well as between MRT and MRTss are also discussed and illustrated with simulated data. In addition, a method for estimating the central volume of distribution of the bound drug and the sum of the central volume of distribution of the unbound drug and the area under the first moment curve of distribution function for drugs with nonlinear protein binding is proposed and illustrated with both simulated and published data.

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