NDLI: Optimal Design for Multivariate Response Pharmacokinetic Models

Content Provider	Springer Nature Link
Author	Gueorguieva, Ivelina Aarons, Leon Ogungbenro, Kayode Jorga, Karin M. Rodgers, Trudy Rowland, Malcolm
Copyright Year	2006
Abstract	We address the problem of designing pharmacokinetic experiments in multivariate response situations. Criteria, based on the Fisher information matrix, whose inverse according to the Rao–Cramer inequality is the lower bound of the variance–covariance matrix of any unbiased estimator of the parameters, have previously been developed for univariate response for an individual and a population. We extend these criteria to design individual and population studies where more than one response is measured, for example, when both parent drug and metabolites are measured in plasma, multi-compartment models, where measurements are taken at more than one site, or when drug concentration and pharmacodynamic data are collected simultaneously. We assume that measurements made at distinct times are independent, but measurements made of each concentration are correlated with a response variance–covariance matrix. We investigated a number of optimisation algorithms, namely simplex, exchange, adaptive random search, simulated annealing and a hybrid, to maximise the determinant of the Fisher information matrix as required by the D-optimality criterion. The multiresponse optimal design methodology developed was applied in two case studies, where the aim was to suggest optimal sampling times. The first was a restrospective iv infusion experiment aimed to characterise the disposition kinetics of tolcapone and its two metabolites in healthy volunteers. The second was a prospective iv bolus experiment designed to estimate the tissue disposition kinetics of eight beta-blockers in rat.
Starting Page	97
Ending Page	124
Page Count	28
File Format	PDF
ISSN	1567567X
Journal	Journal of Pharmacokinetics and Pharmacodynamics
Volume Number	33
Issue Number	2
e-ISSN	15738744
Language	English
Publisher	Springer US
Publisher Date	2006-03-21
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	D-optimal design multiresponse situations multivariate response pharmacokinetic parameters beta-blockers tolcapone physiologically based pharmacokinetic models. Biochemistry Biomedical Engineering Veterinary Medicine Pharmacy Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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