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Title of Journal: Journal of Pharmacokinetics and Biopharmaceutics

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Abbravation: Journal of Pharmacokinetics and Biopharmaceutics

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Kluwer Academic Publishers-Plenum Publishers

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10.1007/bf01366776

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0090-466X

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Simulation for population analysis of MichaelisMe

Authors: Yukiya Hashimoto Toshiko Koue Yuko Otsuki Masato Yasuhara Ryohei Hori Kenichi Inui
Publish Date: 1995/05/23
Volume: 23, Issue: 2, Pages: 205-216
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Abstract

A simulation study was conducted to compare the cost and performance of various models for population analysis of the steady state pharmacokinetic data arising from a onecompartment model with MichaelisMenten elimination The usual MichaelisMenten model MM and its variants provide no estimate of the volume of distribution and generally give poor estimates of the maximal elimination rate and the MichaelisMenten constant The exact solution to the MichaelisMenten differential equation TRUE requires a precise analysis method designed for estimation of population pharmacokinetic parameters the firstorder conditional estimation method and also considerable computational time to estimate population mean parameters accurately The onecompartment model with dosedependent clearance DDCL in conjunction with the firstorder conditional estimation or Laplacian method ran approximately 20fold faster than TRUE and gave accurate population mean parameters for a drug having a long biological halflife relative to the dosing interval These findings suggest that the wellknown MM and its variants should be used carefully for the analysis of blood concentrations of a drug with MichaelisMenten elimination kinetics and that TRUE in conjunction with a precise analysis method should be considered for estimating population pharmacokinetic parameters In addition DDCL is a promising alternative to TRUE with respect to computation time when the dosing interval is short relative to the biological halflife of a drug

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  2. Quinidine pharmacokinetics in man: Choice of a disposition model and absolute bioavailability studies
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  9. Pharmacokinetics and bioavailability of intravenous, oral, and rectal nitrazepam in humans
  10. Application of optimal sampling theory to the determination of metacycline pharmacokinetic parameters: Effect of model misspecification
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  13. Pharmacokinetics of teicoplanin in man after intravenous administration
  14. Theoretical considerations in the calculation of bioavailability of drugs exhibiting Michaelis-Menten elimination kinetics
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