Pharmacokinetics of intravenously administered 125I-labelled human alpha 1-acid glycoprotein

Clinical Pharmacokinetics
F BréeJ P Tillement

Abstract

The volumes of distribution of many acidic drugs have been shown to be close to that of their binding protein, i.e. serum albumin. The distribution of basic drugs mainly bound to alpha 1-acid glycoprotein (AAG) can be questioned with respect to its dependency upon the distribution of this plasma protein. So, a pharmacokinetic study was performed in 7 subjects with human 125I-labelled alpha 1-acid glycoprotein. The steady-state volume of distribution was found to be 5.37 +/- 0.82L. The central volume was 3.23 +/- 0.33L, close to that of plasma volume and the peripheral volume was 2.14 +/- 0.63L. These data allowed the establishment of an equation giving access to the volume of distribution of a basic drug by relating its unbound fraction to physiological distribution of alpha 1-acid glycoprotein. The values yielded by this equation show that the actual and calculated volumes of distribution of basic drugs mainly bound to AAG are discrepant. This protein is thus not the main factor controlling the distribution of basic drugs within the body.

Citations

Feb 24, 2009·European Journal of Drug Metabolism and Pharmacokinetics·Christine Tesseromatis, Anastasia Alevizou
Dec 30, 2018·Pharmaceutical Research·Sherri A Smith, Nigel J Waters
Apr 6, 2019·Current Protein & Peptide Science·Fabrizio Ceciliani, Cristina Lecchi
Jan 7, 2011·Journal of Clinical Pharmacology·Ighovwerha OfotokunEdward P Acosta
Feb 1, 1993·Journal of Pharmacokinetics and Biopharmaceutics·A Aubrée-LecatD Domurado
Aug 11, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Andreas Mats Svennebring
Feb 1, 1987·Journal of Pharmaceutical Sciences·D E KeylerD B Haughey

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