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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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Birkhäuser-Verlag

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DOI

10.1002/sec.965

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0090-466X

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Mathematical model forEmphasis Type="Italic"in v

Authors: Patrice Francheteau JeanLouis Steimer Claude Dubray Daniele Lavene
Publish Date: 1991/06/01
Volume: 19, Issue: 3, Pages: 287-309
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Abstract

We propose a general pharmacokineticpharmacodynamic model that integrates the rhythmic fluctuation of hormone secretion for the description of the hormonelowering effect of a drug The mathematical model takes into account the variation in response observed after administration of a placebo and the drug It is assumed that the change with time in the physiological response during the placebo period results from fluctuations in the concentration of hypothetical endogenous molecules The mathematical formulation for predicting the response after drug intake is derived assuming competitive interaction of these “molecules” with the active species for binding to receptors The suggested “fluctuation model” was implemented in order to describe the time course of the prolactin PRL plasma level after administration of two oral doses 25 and 50 mg of the dopaminomimetic compound DCN 203–922 DCN to 9 healthy male subjects Its perform ance was compared with that of conventional modeling approaches in which the circadian changes after placebo are neglected and the hormone baseline is assumed to be constant The new model provided a better description of the time course of PRL in most subjects It was used for prediction of the amplitude and duration of the PRL suppressant effect after single and chronic administration of DCN at various dosage regimens as well as after changes in drug absorption

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  1. Influence of plasma protein binding kinetics on hepatic clearance assessed from a “tube” model and a “well-stirred” model
  2. Quinidine pharmacokinetics in man: Choice of a disposition model and absolute bioavailability studies
  3. Effect of plasma protein and tissue binding on the time course of drug concentration in plasma
  4. A nonlinear mixed-effects pharmacokinetic model comparing two formulations of cyclosporine in stable renal transplant patients
  5. Linear pharmacokinetic models: Geometric construction to determine transfer and elimination rate constants
  6. Modeling of drug response in individual subjects
  7. Prediction of diazepam disposition in the rat and man by a physiologically based pharmacokinetic model
  8. Pharmacokinetics of piroxicam, a new nonsteroidal anti-inflammatory agent, under fasting and postprandial states in man
  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
  11. Estimation of drug binding parameters
  12. Relationship between plasma or serum drug concentration and amount of drug in the body at steady state upon multiple dosing
  13. Pharmacokinetics of teicoplanin in man after intravenous administration
  14. Theoretical considerations in the calculation of bioavailability of drugs exhibiting Michaelis-Menten elimination kinetics
  15. Mathematical model for in vivo pharmacodynamics integrating fluctuation of the response: Application to the prolactin suppressant effect of the dopaminomimetic drug DCN 203–922
  16. Simulation for population analysis of Michaelis-Menten elimination kinetics
  17. Pharmacodynamic modeling of the in vitro vasodilating effects of organic mononitrates
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