Abstract
Pooling of Michaelis-Menten equations for models having parallel paths for formation of two or more metabolites is discussed. A theory which explains phenomena exhibited by pooled nonlinear pharmacokinetic systems and equations relating pooled Michaelis-Menten constants (V p ,K p )to microscopic constants (V i ,K i )are presented. The suitability of this type of pooling for use in pharmacokinetic modeling is also discussed. Use of pooling concepts in the design of clinical studies is demonstrated.
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References
F. Lundquist and H. Wolthers. The kinetics of alcohol elimination in man.Acta Pharmacol. Toxicol. 14: 265–289 (1958).
G. Levy. Pharmacokinetics of salicylate elimination in man.J. Pharm. Sci. 54: 959–967 (1965).
G. Levy, T. Tsuchiya, and L. P. Amsel. Limited capacity for salicyl phenolic glucuronide formation and its effect on the kinetics of salicylate elimination in man.Clin. Pharmacol. Therap. 13: 258–268 (1972).
N. Gerber and J. G. Wagner. Explanation of dose dependent decline of diphenylhydantoin plasma levels by fitting to the integrated form of the Michaelis-Menten equation.Res. Commun. Chem. Pathol. Pharmacol. 3: 455–466 (1972).
J. G. Wagner and J. A. Patel. Variations in absorption and elimination rates of ethyl alcohol in a single subject.Res. Commun. Chem. Pathol. Pharmacol. 4: 61–76 (1972).
J. G. Wagner, Properties of the Michaelis-Menten equation and its integrated form which are useful in pharmacokinetics.J. Pharmacokin. Biopharm. 1: 103–121 (1973).
J. L. Neal. Analysis of Michaelis kinetics for two independent saturable membrane transport functions.J. Theoret. Biol. 35: 113–118 (1972).
G. Spears, J. G. T. Sneyd, and E. G. Loten. A method for deriving kinetic constants for two enzymes acting on the same substrate.Biochem. J. 125: 1149–1151 (1971).
R. E. Hillman, I. Albrecht, and L. E. Rosenberg. Identification and analysis of multiple glycine transport systems in isolated mammalian renal tubules.J. Biol. Chem. 243: 5566–5571 (1968).
C. R. Schriver and F. Mohyuddin. Amino acid transport in kidney.J. Biol. Chem. 243: 3207–3213 (1968).
R. L. Dedrick and D. D. Forrester. Blood flow limitations in interpreting Michaelis constants for ethanol oxidationin vivo.J. Biochem. Pharmacol. 22: 1133–1140 (1973).
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Supported in part by Public Health Service Grant 5-P11-GM15559.
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Sedman, A.J., Wagner, J.G. Quantitative pooling of Michaelis-Menten equations in models with parallel metabolite formation paths. Journal of Pharmacokinetics and Biopharmaceutics 2, 149–160 (1974). https://doi.org/10.1007/BF01061505
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DOI: https://doi.org/10.1007/BF01061505