Application of the optimal design approach to improve a pretransplant drug dose finding design for ciclosporin

Hennig, Stefanie, Nyberg, Joakim, Fanta, Samuel, Backman, Janne T., Hoppu, Kalle, Hooker, Andrew C. and Karlsson, Mats O. (2011) Application of the optimal design approach to improve a pretransplant drug dose finding design for ciclosporin. Journal of Clinical Pharmacology, 52 3: 347-360. doi:10.1177/0091270010397731


Author Hennig, Stefanie
Nyberg, Joakim
Fanta, Samuel
Backman, Janne T.
Hoppu, Kalle
Hooker, Andrew C.
Karlsson, Mats O.
Title Application of the optimal design approach to improve a pretransplant drug dose finding design for ciclosporin
Journal name Journal of Clinical Pharmacology   Check publisher's open access policy
ISSN 0091-2700
1552-4604
Publication date 2011-01-01
Sub-type Article (original research)
DOI 10.1177/0091270010397731
Volume 52
Issue 3
Start page 347
End page 360
Total pages 14
Place of publication Thousand Oaks, CA, United States
Publisher Sage Publications
Collection year 2012
Language eng
Abstract A time and sampling intensive pretransplant test dose design was to be reduced, but at the same time optimized so that there was no loss in the precision of predicting the individual pharmacokinetic (PK) estimates of posttransplant dosing. The following variables were optimized simultaneously: sampling times, ciclosporin dose, time of second dose, infusion duration, and administration order, using a published ciclosporin population PK model as prior information. The original design was reduced from 22 samples to 6 samples/patient and both doses (intravenous oral) were administered within 8 hours. Compared with the prior information given by the published ciclosporin population PK model, the expected standard deviations (SDs) of the individual parameters for clearance and bioavailability could be reduced by, on average, 40% under the optimized sparse designs. The gain of performing the original rich design compared with the optimal reduced design, considering the standard errors of the parameter estimates, was found to be minimal. This application demonstrates, in a practical clinical scenario, how optimal design techniques may be used to improve diagnostic procedures given available software and methods.
Keyword Ciclosporin
Therapeutic drug monitoring
Optimal design
Diagnostics
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes Published online before print May 4, 2011.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Pharmacy Publications
 
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Created: Mon, 23 May 2011, 18:27:42 EST by Dr Stefanie Hennig on behalf of School of Pharmacy