Correlation betweenin vitro andin vivo drug metabolism rate: Oxidation of ethoxybenzamide in rat

  • Jiunn Huei Lin
  • Masahiro Hayashi
  • Shoji Awazu
  • Manabu Hanano


In vitroand in vivocorrelations of the microsomal oxidation of drugs were examined, using ethoxybenzamide as a model drug. Ethoxybenzamide disappearance time course from rat plasma in vivowas analyzed by a two-compartment model assuming a Michaelis-Menten type elimination process. Ethoxybenazmide oxidation in vitrowas measured by the appearance rate of salicylamide in rat liver microsomal suspension. Parameters obtained were Vmax=3.46 and 3.77 μmoles/min/kg body weight and Km=0.378 and 0.192mM, in vitroand in vivo,respectively.

Key words

in vitro andin vivo correlation microsomal oxidation of drugs nonlinear pharmacokinetics physiological pharmacokinetics tissue distribution distribution volume ethoxybenzamide Michaelis-Menten parameters 


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  1. 1.
    G. R. Wilkinson. Pharmacokinetics of drug disposition: Hemodynamic considerations.Ann. Rev. Pharmacol. 15:11–27 (1975).PubMedCrossRefGoogle Scholar
  2. 2.
    R. L. Dedrick. Animal-scale-up.J. Pharmacokin. Biopharm. 1:435–461 (1973).CrossRefGoogle Scholar
  3. 3.
    R. L. Dedrick, D. D. Forrester, and D. H. W. Ho.In vitro-in vivo correlation of drug metabolism-deamination of 1-β-D-arabinofuranosylcytosine.Biochem. Pharmacol. 21:1–16 (1972).PubMedCrossRefGoogle Scholar
  4. 4.
    A. B. Makar and G. J. Mannering. Kinetics of ethanol metabolism in the intact rat and monkey.Biochem. Pharmacol. 19:2017–2022 (1970).PubMedCrossRefGoogle Scholar
  5. 5.
    R. L. Dedrick and D. D. Forrester. Blood flow limitations in interpreting Michaelis constants for ethanol oxidationin vivo.Biochem. Pharmacol. 22:1133–1140 (1973).PubMedCrossRefGoogle Scholar
  6. 6.
    H. Nogami, M. Hanano, S. Awazu, and H. H. Moon. Pharmacokinetic analysis on the disappearance of ethoxybenzamide from plasma: Statistical treatment of data of two compartmental model by a digital computer.Chem. Pharm. Bull. (Tokyo) 17:2097–2104 (1969).CrossRefGoogle Scholar
  7. 7.
    G. Levy and T. Matsuzawa. Pharmacokinetics of salicylamide elimination in man.Pharmacol. Exp. Ther. 156:285–293 (1967).Google Scholar
  8. 8.
    S. Awazu, M. Hanano, H. H. Moon, T. Fuwa, T. Iga, and H. Nogami. Pharmacokinetic analysis by digital computer [in Japanese]. In K. Kakemi (ed.),Absorption, Metabolism, and Excretion of Drugs. Hirokawa Publishing Co., Tokyo, 1971, pp. 301–332.Google Scholar
  9. 9.
    S. Awazu. Analogue and digital computer [in Japanese]. In K. Tsuda and H. Nogami (eds.),Biopharmacy, Chijin Shokan, Tokyo, 1971, pp. 448–489.Google Scholar
  10. 10.
    H. G. Boxenbaum, S. Riegelman, and R. M. Elashoff. Statistical estimations in phar-macokinetics.J. Pharmacokin. Biopharm. 2:123–148 (1974).CrossRefGoogle Scholar
  11. 11.
    R. Grundin, P. Moldéus, S. Orrenius, K. O. Borg, I. Skanberg, and C. von Bahr. The possible role of cytochrome P-450 in the liver “first pass elimination” of aβ-receptor blocking drug.Acta Pharmacol. Toxicol. 35:242–260 (1974).CrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1978

Authors and Affiliations

  • Jiunn Huei Lin
    • 1
  • Masahiro Hayashi
    • 1
  • Shoji Awazu
    • 1
  • Manabu Hanano
    • 1
  1. 1.Faculty of Pharmaceutical SciencesUniversity of TokyoTokyoJapan

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