Estimation of population characteristics of pharmacokinetic parameters from routine clinical data

  title={Estimation of population characteristics of pharmacokinetic parameters from routine clinical data},
  author={Lewis B. Sheiner and Barr Rosenberg and Vinay V. Marathe},
  journal={Journal of Pharmacokinetics and Biopharmaceutics},
A general data analysis technique estimates average population values of pharmacokinetic parameters and their interindividual variability from clinical pharmacokinetic data gathered during the routine care of patients. Several drug concentration values from each individual, along with dosage information and the values of other routinely assessed variables suffice for purposes of analysis. The Maximum Likelihood principle estimates underlying population values without the necessity for the… 

Estimation of pharmacokinetic parameters based on the patient-adjusted population data.

  • R. Mehvar
  • Medicine, Biology
    American journal of pharmaceutical education
  • 2006
The 2 main methods of obtaining population kinetic data, namely the two-stage method and nonlinear mixed effect model, and their applications to the pharmacokinetic-based design of dosage regimens are described.

Evaluation of methods for estimating population pharmacokinetic parameters. III. Monoexponential model: Routine clinical pharmacokinetic data

  • L. SheinerS. Beal
  • Biology, Medicine
    Journal of Pharmacokinetics and Biopharmaceutics
  • 2005
Evidence is provided of NONMEM's validity and usefulness by comparing both approaches on simulated routine-type pharmacokinetic data arising from a monoexponential model by comparing the estimates of population parameters provided by the STS method.

Evaluation of methods for estimating population pharmacokinetic parameters. I. Michaelis-menten model: Routine clinical pharmacokinetic data

Individual pharmacokinetic parameters quantify the pharmacokinetics of an individual, while population pharmacokinetic parameters quantify population mean kinetics, interindividual variability, and

Pitfalls and valid approaches to pharmacokinetic analysis of mean concentration data following intravenous administration

The area under the mean data curve calculated via the linear trapezoidal rule from time zero to the last detectable concentration sampling point is equal to the mean of the individual subject areas under the curve for the same time span, which supports the use of mean data for determination of model-independent pharmacokinetic parameters.

SOP 14: Population Pharmacokinetic Analysis

  • Biology, Medicine
    Oncology Research and Treatment
  • 2003
This document concentrates on standard procedures for data analysis of population pharmacokinetic analyses, particularly useful with data which are obtained under incompletely controlled conditions in clinical routine care.

Evaluation of population (NONMEM) pharmacokinetic parameter estimates

It is proposed that generally available program packages performing estimation of the pharmacokinetic parameters from observational data should contain the necessary software to evaluate the reliability of the parameter estimates on a second data set.


OPT uses prior information on the distribution of population pharmacokinetic parameters and plasma drug concentration measurements to obtain the 'most likely' set of parameters for the individual.

Bayesian estimation of pharmacokinetic parameters: an important component to include in the teaching of clinical pharmacokinetics and therapeutic drug monitoring

The literature was scanned using Pubmed to provide background into the Bayesian method and an Add-in for Excel program was used to show the ability of the method to estimate PKP using sparse blood fluid concentration vs time data.

An evaluation of point and interval estimates in population pharmacokinetics using Nonmem analysis

In a simulation study of the estimation of population pharmacokinetic parameters, including fixed and random effects, the estimates and confidence intervals produced by NONMEM were evaluated and standard error estimates are appropriate as estimates of standard deviation when the underlying variability is small.



Modelling of individual pharmacokinetics for computer-aided drug dosage.

DifFerences in serum digoxin concentrations between outpatients and inpatients: An effect of compliance?

Using the technique of data analysis suggested in this paper and periodic measurement of serum digoxin concentrations, individual compliance and its consistency over time can be assessed and such information may assist in patient management.

Pharmacokinetics of digoxin: Comparison of a two- and a three-compartment model in man

It was demonstrated that the three-compartment open model is the simplest pharmacokinetic model consistent with the data observed in this experiment, and resulted in a statistically significant reduction in residual error, a marked improvement in the randomness of scatter of the experimental data about the serum digoxin-time curve, and better agreement of the predicted serum concentration-time Curve.

Correlation of plasma levels of digoxin in cardiac patients with dose and measures of renal function

It is found that these parameters do not allow accurate prediction of PDC's in the individual patient, based on data collected in a panel of cardiac patients, and Serial measurements of P DC's are therefore necessary in individual patients taking digoxin.

Digoxin pharmacokinetics: Role of renal failure in dosage regimen design

Radioimmunoassayed serum concentration and urinary excretion data for digoxin from azotemic patients were characterized using a 2‐compartment open model and a model‐independent approach to calculation of maintenance doses of digoxin was developed.

Instructional goals for physicians in the use of blood level data—and the contribution of computers

A syllabus has been outlined for the teaching of the qualitative aspects of pharmacokinetics (stripped of the mathematical procedures for deriving the formulas) to physicians as well as house staff and medical students.

Pharmacokinetic Design of Digoxin Dosage Regimens in Relation to Renal Function

T HE incidence of adverse effects during empirical therapy with digoxin (that is, therapy without monitoring serum concentrations of digoxin) has been assessed as 18 per cent ill the general medical

Digoxin pharmacokinetics: multicompartmental analysis and its clinical implications.

A three compartment open kinetic model has been proposed as the simplest model consistent with the plasma, urinary and faecal data obtained and can be derived from a simple formula based on the glomerular filtration rate, extra-renal clearance and bioavailability of the digoxin preparation used.

A new simple and rapid method to monitor the renal function based on pharmacokinetic consideration of endogeneous creatinine

Almost a perfect prediction of the status of renal function in two anephric patients was demonstrated using the proposed equation, which would enable on to monitor the creatinine clearance on an hourly basis.