2008 - Marseille - France

PAGE 2008: Methodology- Design
Kayode Ogungbenro

An Effective approach for Obtaining Optimal Sampling Windows for Population Pharmacokinetic Experiments

Kayode Ogungbenro1 and Leon Aarons2

1Centre for Applied Pharmacokinetic Research, 2School of Pharmacy and Pharmaceutical Sciences, The University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom

Objectives: To describe a new approach for optimising sampling windows lengths for population pharmacokinetic experiments.  The approach should be applicable to both continuous and exact population designs and the sampling windows obtained should achieve two objectives: the joint efficiency of the sampling windows design should attain the specified level and the sampling windows should also reflect the sensitivities of the plasma concentration-time profile to the parameters.

Methods: Sampling windows were obtained using a three stage approach.  At the first stage, a fixed D-optimal sampling design was obtained.  At the second stage, conditional sampling windows were obtained around the fixed D-optimal time points using the quadratic loss function by allowing the sampling windows design to result in a specified loss of efficiency when compared to the fixed D-optimal time points.  At the final stage, the sampling windows design was evaluated and the lengths modified by equal percentage until the desired efficiency levels is attained.  This approach was applied to an example and the results compared with two existing methods: Graham and Aarons [1] and Duffull et al [2] approaches.  Simulations were also conducted.

Results: The results obtained from simulations showed that the sampling windows obtained with this approach are comparable to fixed D-optimal time points in terms of bias and precision with which the parameters are estimated.  The results also showed that the approach produced narrower window where the plasma concentration-time profile is more sensitive to parameters and wider window where there is less sensitivity.

Conclusions: Sampling windows offers flexibility in terms of sampling times and still provides data that are informative and a new effective approach has been described.

[1] Graham G, Aarons L. Optimal blood sampling time windows for parameter estimation in population pharmacokinetic experiments. Statistics in Medicine, 2006; 25: 4004-4019.
[2] Duffull SB, Mentrť F, Aarons L. Optimal design of a population pharmacodynamic experiment for ivabradine. Pharmaceutical Research, 2001; 18: 83-89.

Reference: PAGE 17 (2008) Abstr 1362 [www.page-meeting.org/?abstract=1362]
Poster: Methodology- Design