Abstract
Throughout the literature, enzyme constants have been derived by utilizing in vivodata and indirectly assuming that these data were described by the one-compartment open model. However, many drugs are probably best described by a two-compartment open model with Michaelis-Menten elimination kinetics. Simulated data, which obey the two-compartment open model with Michaelis-Menten elimination, and which illustrate some of the interesting properties of such models, are presented. Treatment of two-compartment data by one-compartment analysis is shown to result in a serious distortion of enzyme parameters (V m ,K m ).For data which obey the two-compartment open model, estimation of the Michaelis-Menten constant (K m )and the maximum velocity (V m )by one-compartment analysis cannot be theoretically justified and therefore should be avoided.
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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. Importance of the use of the appropriate pharmacokinetic model to analyzein vivo enzyme constants. Journal of Pharmacokinetics and Biopharmaceutics 2, 161–173 (1974). https://doi.org/10.1007/BF01061506
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DOI: https://doi.org/10.1007/BF01061506