The Role of Unbound Drug in Pharmacokinetics/Pharmacodynamics and in Therapy
| Autor: | Nerea Leal, John C. Lukas, Rosario Calvo, Elena Suarez, Monica Rodriguez |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Drug
media_common.quotation_subject Population Antineoplastic Agents HIV Infections Plasma protein binding Pharmacology Models Biological Species Specificity Pharmacokinetics Neoplasms Drug Discovery Animals Humans education Serum Albumin PK/PD models media_common education.field_of_study Chemistry Biological activity Blood Proteins Orosomucoid In vitro Anti-Retroviral Agents Pharmacodynamics Models Animal Drug Monitoring Protein Binding |
| Zdroj: | Current Pharmaceutical Design. 12:977-987 |
| ISSN: | 1381-6128 |
| DOI: | 10.2174/138161206776055967 |
| Popis: | The evolution of research on drug protein binding is discussed with the unbound concentration (Cu) and the unbound fraction (fu) as protagonists. Particular attention is paid to the mechanisms via which alterations in binding affect the pharmacokinetics (PK) and the effect, or independently the pharmacodynamics (PD). Apart from albumin, the important alpha-acid glycoprotein (AGP), as well as specific drug classes and applications in the clinic and development (routine monitoring, cancer and HIV therapy, allometry) are addressed. The flaws with the classical method of indirectly calculating the Cu or the unbound PK/PD parameters, based on the fu in vitro, are related to the intrinsic complexity and variability in the outcomes. Increased focus is urged on directly estimating the unbound PK/PD and also on using population statistical methods. |
| Databáze: | OpenAIRE |
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