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Reduced and optimiz...
Reduced and optimized trial designs for drugs described by a target mediated drug disposition model
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- Brekkan, Ari (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Jönsson, Siv, 1963- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Karlsson, Mats O (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Hooker, Andrew, 1973- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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(creator_code:org_t)
- 2018-06-08
- 2018
- Engelska.
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Ingår i: Journal of Pharmacokinetics and Pharmacodynamics. - : SPRINGER/PLENUM PUBLISHERS. - 1567-567X .- 1573-8744. ; 45:4, s. 637-647
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Abstract
Ämnesord
Stäng
- Monoclonal antibodies against soluble targets are often rich and include the sampling of multiple analytes over a lengthy period of time. Predictive models built on data obtained in such studies can be useful in all drug development phases. If adequate model predictions can be maintained with a reduced design (e.g. fewer samples or shorter duration) the use of such designs may be advocated. The effect of reducing and optimizing a rich design based on a published study for Omalizumab (OMA) was evaluated as an example. OMA pharmacokinetics were characterized using a target-mediated drug disposition model considering the binding of OMA to free IgE and the subsequent formation of an OMA-IgE complex. The performance of the reduced and optimized designs was evaluated with respect to: efficiency, parameter uncertainty and predictions of free target. It was possible to reduce the number of samples in the study by 30% while still maintaining an efficiency of almost 90%. A reduction in sampling duration by two-thirds resulted in an efficiency of 75%. Omission of any analyte measurement or a reduction of the number of dose levels was detrimental to the efficiency of the designs (efficiency ae 51%). However, other metrics were, in some cases, relatively unaffected, showing that multiple metrics may be needed to obtain balanced assessments of design performance.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- Optimal design
- Target mediated drug disposition
- Monoclonal antibodies
- Sampling time optimization
- Model-based
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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