Kinetics of pharmacologic response. I. Proposed relationships between response and drug concentration in the intact animal and man.

  title={Kinetics of pharmacologic response. I. Proposed relationships between response and drug concentration in the intact animal and man.},
  author={John G. Wagner},
  journal={Journal of theoretical biology},
  volume={20 2},
  • J. Wagner
  • Published 1 August 1968
  • Biology
  • Journal of theoretical biology
An interpretation of the Hill equation: time course of diuretic response after furosemide administration in man.
The Hill equation, which has been widely used without a definite rationale, for correlation between pharmacologic response intensity and drug concentration is revealed as an approximate equation of the response function.
Understanding the Dose-Effect Relationship
The design of rational dosing regimens for clinical therapeutics cannot be performed with a knowledge of pharmacokinelics alone, and the linking of pharmacokinetics and pharmacodynamics to predict firstly the dose-concentration, and then the concentration-effect relationship is required.
A modern view of pharmacokinetics
  • J. Wagner
  • Biology, Medicine
    Journal of Pharmacokinetics and Biopharmaceutics
  • 2005
This paper contains references to over 160 articles which suggest evidence on nonlinearities in drug absorption, distribution, metabolism and excretion, and the pharmacokinetics of drug action, which are reviewed in a format of six tables.
The pharmacokinetic bases of biological response quantification in toxicology, pharmacology and pharmacodynamics.
  • E. R. Garrett
  • Biology, Medicine
    Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques
  • 1977
The time courses of blood levels, tissue levels and amounts excreted of an administered drug and its formed metabolites can be monitored simultaneously with observed pharmacological, toxicological or
The use of kinetic-dynamic interactions in the evaluation of drugs
This review shows, with reference to psychotropic drugs, how, in simple terms, it is possible to relate pharmacokinetics with pharmacodynamics, and how such relationships may provide a greater insight into drug activity and enhance drug development.
Molecular Mechanisms of Drug Action and Pharmacokinetic-Pharmacodynamic Models
The predictive potential of the pharmacokinetic-pharmacodynamic models should prove useful in evaluating pharmaceutical formulations with controlled drug delivery.
Drug-absorption analysis from pharmacological data. I. Method and confirmation exemplified for the mydriatic drug tropicamide.
It is demonstrated that through the suitable use of intravenous dose-effect curves, the postulation of hypothetical models for pharmacon-receptor site interaction is obviated and the relationship between the quantity of drug in body compartments (biophase) and the observed intensity of drug response is graphically provided.
Application of effect-compartment model to bumetanide-indomethacin interaction in dogs
An expanded pharmaco-dynamic model has been introduced in which the hypothetical effect compartment is linked, by a first-order process (Kue),to the urine compartment, and accommodates bumetanide's luminal site of action in the kidney tubule as well as the drug's temporal component.
The Efficiency Concept in Pharmacodynamics
It is concluded that the shape of the time course of drug presentation to its site of action is an independent determinant of overall response and the possibility of adjusting the drug input profile to maximise therapeutic effect per dose should be considered in designing administration schedules and in drug development.


Kinetics of pharmacologic effects
  • G. Levy
  • Medicine, Biology
    Clinical pharmacology and therapeutics
  • 1966
Pharmacokinetic analysis of pharmacologic activity data can lead to better understanding of the relationship between dose and the multiple pharmacologic effects elicited by a drug, and it can facilitate the assessment of factors which account for individual variations in the response to drugs.
Blood Levels of Drug at the Equilibrium State after Multiple Dosing
THERE is ample evidence1–20 that when a fixed dose of drug is administered in a fixed multiple-dose regimen, the blood levels of drug eventually reach a steady state in which the blood level time
  • G. Levy
  • Medicine
    British journal of anaesthesia
  • 1964
SUMMARY It is shown on theoretical grounds that, assuming tubocurarine elimination is an exponential process and the intensity of its pharmacological activity is proportional to the logarithm of the
The Determination of Enzyme Dissociation Constants
On the basis of the assumed theory the rate of the observed reaction is directly proportional to the concentration of the enzyme-substrate compound, (ES), a t all values of the concentration of the
Apparent Potentiating Effect of a Second Dose of Drug
The purpose of this communication is to suggest a pharmacokinetic basis for this apparent potentiation of a drug after its apparent disappearance.