Modeling of Pharmacokinetics and Pharmacodynamics with Application to Cancer and Arthritis

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2012
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urn:nbn:de:bsz:352-194726
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Abstract
Mathematical modeling of pharmacokinetics / pharmacodynamics (PKPD) is an important and growing field in drug development. In this work we develop preclinical PKPD models based on fundamental biological and pharmacological principles.

Equipped with a PKPD model, different dosing schedules could be simulated and therefore, a valuable contribution to first in human dose selection could be achieved. We consider different mathematical model figures and discuss the properties and biological basis. Such tools serve as modules for a final PKPD model. We apply ordinary and delay differential equations and especially focus on modeling of delays and lifespans in populations. We show a fundamental relationship between transit compartments and lifespan models. Moreover, we investigate the weighted least squares estimator and derive statistical characteristics of model parameter.

We present a PKPD model to describe tumor growth and anticancer effects for mono- and combination therapy. Further, we construct a PKPD model for arthritis development and antibody effects.

Summarizing, we develop (semi)-mechanistic mathematical PKPD models based on pharmacological assumptions and apply our models to measured data from preclinical phase.
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310 Statistics
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ISO 690KOCH, Gilbert, 2012. Modeling of Pharmacokinetics and Pharmacodynamics with Application to Cancer and Arthritis [Dissertation]. Konstanz: University of Konstanz
BibTex
@phdthesis{Koch2012Model-19472,
  year={2012},
  title={Modeling of Pharmacokinetics and Pharmacodynamics with Application to Cancer and Arthritis},
  author={Koch, Gilbert},
  address={Konstanz},
  school={Universität Konstanz}
}
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    <dcterms:abstract xml:lang="eng">Mathematical modeling of pharmacokinetics / pharmacodynamics (PKPD) is an important and growing field in drug development. In this work we develop preclinical PKPD models based on fundamental biological and pharmacological principles.&lt;br /&gt;&lt;br /&gt;Equipped with a PKPD model, different dosing schedules could be simulated and therefore, a valuable contribution to first in human dose selection could be achieved. We consider different mathematical model figures and discuss the properties and biological basis. Such tools serve as modules for a final PKPD model. We apply ordinary and delay differential equations and especially focus on modeling of delays and lifespans in populations. We show a fundamental relationship between transit compartments and lifespan models. Moreover, we investigate the weighted least squares estimator and derive statistical characteristics of model parameter.&lt;br /&gt;&lt;br /&gt;We present a PKPD model to describe tumor growth and anticancer effects for mono- and combination therapy. Further, we construct a PKPD model for arthritis development and antibody effects.&lt;br /&gt;&lt;br /&gt;Summarizing, we develop (semi)-mechanistic mathematical PKPD models based on pharmacological assumptions and apply our models to measured data from preclinical phase.</dcterms:abstract>
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May 25, 2012
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