Evolución temporal de la respuesta farmacoterapéutica: integración de modelos farmacocinéticos y farmacodinámicos (II) / The curse of pharmacotherapeutic response: integration pharmacokinetic and pharmacodynamic models (II)

RESUMEN

En la primera parte de este artículo de revisión, se han presentado los modelos farmacodinámicos básicos cuyo conocimiento es imprescindible para establecer las bases de la modelización farmacocinética-farmacodinámica. En esta segunda parte, se inicia la presentación de los modelos PK/PD. Cuando el efecto farmacológico máximo se presenta diferido en el tiempo respecto al que se alcanza la concentración plasmática máxima, los modelos farmacodinámicos directos, no son capaces de describir el comportamiento dinámico de los fármacos. En estos casos, el modelo del compartimento del efecto y/o los modelos de respuestas indirectas entre otros pueden utilizarse para integrar el conocimiento cinético y dinámico del fármaco

ABSTRACT

Nowadays, the integration of pharmacokinetics and pharmacodynamics concepts is considered as an essential tool to increase the efficiency of clinical trial and a strategy to improve the rational use of medicines. This review presents a description of pharmacokinetics- pharmacodynamics compartimental models that can describe the time course of the clinical endpoints and surrogate markers in subjects receiving pharmacological treatment. In the first part of this review the basic pharmacokinetic models that directly relate drug concentrations to clinical effect are presented together with examples. In the second part we described the pharmacokinetic-pharmacodynamic models used to model the delay observed between plasma concentrations and clinical response. In particular, effect compartment model and basic models of indirect responses are presented with examplesIn the first part of this review, the basic pharmacokinetic models that directly relate drug concentrations to clinical effect were presented. They are essentials to lay the foundations of pharmacokinetic-pharmacodynamic models. In this second part, we describe the PK/PD models when a delay between plasma concentrations and clinical response exits. In this situation, direct pharmacodynamics models are not aplicable and the effect compartment model and/or the basic models of indirect responses has been used to integrated the pharmacokinetic and pharmacodynamic knowledge