Application of the Optimal Design Approach to Improve a Pretransplant Drug Dose Finding Design for Ciclosporin
2012 (English)In: Journal of clinical pharmacology, ISSN 0091-2700, E-ISSN 1552-4604, Vol. 52, no 3, 347-360 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2012. Vol. 52, no 3, 347-360 p.
IdentifiersURN: urn:nbn:se:uu:diva-160467DOI: 10.1177/0091270010397731ISI: 000300755600006PubMedID: 21543664OAI: oai:DiVA.org:uu-160467DiVA: diva2:451135