Charles Darwin University

CDU eSpace
Institutional Repository

 
CDU Staff and Student only
 

Towards optimal design of anti-malarial pharmacokinetic studies

Simpson, Julie A., Jamsen, Kris M., Price, Ric N., White, Nicholas J., Lindegardh, Niklas, Tarning, Joel and Duffull, Stephen B. (2009). Towards optimal design of anti-malarial pharmacokinetic studies. Malaria Journal,8(1):1-7.

Document type: Journal Article
Attached Files (Some files may be inaccessible until you login with your CDU eSpace credentials)
Name Description MIMEType Size Downloads
Download this reading Price_8440.pdf Published version application/pdf 277.51KB 76
Reading the attached file works best in Firefox, Chrome and IE 9 or later.

IRMA ID 10202xPUB25
Title Towards optimal design of anti-malarial pharmacokinetic studies
Author Simpson, Julie A.
Jamsen, Kris M.
Price, Ric N.
White, Nicholas J.
Lindegardh, Niklas
Tarning, Joel
Duffull, Stephen B.
Journal Name Malaria Journal
Publication Date 2009
Volume Number 8
Issue Number 1
ISSN 1475-2875   (check CDU catalogue open catalogue search in new window)
Start Page 1
End Page 7
Total Pages 7
Place of Publication London, U.K.
Publisher BioMed Central Ltd.
HERDC Category C1 - Journal Article (DEST)
Abstract Background
Characterization of anti-malarial drug concentration profiles is necessary to optimize dosing, and thereby optimize cure rates and reduce both toxicity and the emergence of resistance. Population pharmacokinetic studies determine the drug concentration time profiles in the target patient populations, including children who have limited sampling options. Currently, population pharmacokinetic studies of anti-malarial drugs are designed based on logistical, financial and ethical constraints, and prior knowledge of the drug concentration time profile. Although these factors are important, the proposed design may be unable to determine the desired pharmacokinetic profile because there was no formal consideration of the complex statistical models used to analyse the drug concentration data.

Methods
Optimal design methods incorporate prior knowledge of the pharmacokinetic profile of the drug, the statistical methods used to analyse data from population pharmacokinetic studies, and also the practical constraints of sampling the patient population. The methods determine the statistical efficiency of the design by evaluating the information of the candidate study design prior to the pharmacokinetic study being conducted.

Results
In a hypothetical population pharmacokinetic study of intravenous artesunate, where the number of patients and blood samples to be assayed was constrained to be 50 and 200 respectively, an evaluation of varying elementary designs using optimal design methods found that the designs with more patients and less samples per patient improved the precision of the pharmacokinetic parameters and inter-patient variability, and the overall statistical efficiency by at least 50%.

Conclusion
Optimal design methods ensure that the proposed study designs for population pharmacokinetic studies are robust and efficient. It is unethical to continue conducting population pharmacokinetic studies when the sampling schedule may be insufficient to estimate precisely the pharmacokinetic profile.
Keywords anti-malarial
pharmacokinetic
DOI http://dx.doi.org/10.1186/1475-2875-8-189   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


© copyright

Every reasonable effort has been made to ensure that permission has been obtained for items included in CDU eSpace. If you believe that your rights have been infringed by this repository, please contact digitisation@cdu.edu.au.

 
Versions
Version Filter Type
Access Statistics: 98 Abstract Views, 77 File Downloads  -  Detailed Statistics
Created: Wed, 03 Mar 2010, 16:49:51 CST