Asset Details
Do you wish to reserve the book?
The use of clinical irrelevance criteria in covariate model building with application to dofetilide pharmacokinetic data
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
The use of clinical irrelevance criteria in covariate model building with application to dofetilide pharmacokinetic data
Do you wish to request the book?
The use of clinical irrelevance criteria in covariate model building with application to dofetilide pharmacokinetic data
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
The use of clinical irrelevance criteria in covariate model building with application to dofetilide pharmacokinetic data
2008
Overview
To characterise the pharmacokinetics of dofetilide in patients and to identify clinically relevant parameter–covariate relationships. To investigate three different modelling strategies in covariate model building using dofetilide as an example: (1) using statistical criteria only or in combination with clinical irrelevance criteria for covariate selection, (2) applying covariate effects on total clearance or separately on non-renal and renal clearances and (3) using separate data sets for covariate selection and parameter estimation. Pooled concentration-time data (1,445 patients, 10,133 observations) from phase III clinical trials was used. A population pharmacokinetic model was developed using NONMEM. Stepwise covariate model building was applied to identify important covariates using the strategies described above. Inclusion and exclusion of covariates using clinical irrelevance was based on reduction in interindividual variability and changes in parameters at the extremes of the covariate distribution. Parametric separation of the elimination pathways was accomplished using creatinine clearance as an indicator of renal function. The pooled data was split in three parts which were used for covariate selection, parameter estimation and evaluation of predictive performance. Parameter estimations were done using the first-order (FO) and the first-order conditional estimation (FOCE) methods. A one-compartment model with first order absorption adequately described the data. Using clinical irrelevance criteria resulted in models containing less parameter–covariate relationships with a minor loss in predictive power. A larger number of covariates were found significant when the elimination was divided into a renal part and a non-renal part, but no gain in predictive power could be seen with this data set. The FO and FOCE estimation methods gave almost identical final covariate model structures with similar predictive performance. Clinical irrelevance criteria may be valuable for practical reasons since stricter inclusion/exclusion criteria shortens the run times of the covariate model building procedure and because only the covariates important for the predictive performance are included in the model.
Publisher
Springer US,Springer Nature B.V
Subject
/ Adult
/ Aged
/ Anti-Arrhythmia Agents - administration & dosage
/ Anti-Arrhythmia Agents - blood
/ Anti-Arrhythmia Agents - pharmacokinetics
/ Biomedical and Life Sciences
/ Biomedical Engineering and Bioengineering
/ Clinical Trials, Phase III as Topic - statistics & numerical data
/ Drug Therapy - statistics & numerical data
/ FARMACI
/ Female
/ Humans
/ Male
/ NONMEM
/ PHARMACY
/ Phenethylamines - administration & dosage
/ Phenethylamines - pharmacokinetics
/ Sulfonamides - administration & dosage
/ Sulfonamides - pharmacokinetics
