The Universally Unrecognized Assumption in Predicting Drug Clearance and Organ Extraction Ratio
| Autor: | Alan R. Wolfe, Leslie Z. Benet, S Liu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Data Interpretation
Metabolic Clearance Rate Extraction ratio Pharmacology Bioinformatics 030226 pharmacology & pharmacy Models Biological Article Dose-Response Relationship 03 medical and health sciences 0302 clinical medicine Pharmacokinetics In vivo Models Medicine Humans Pharmacology (medical) Dosing Pharmacology & Pharmacy Dose-Response Relationship Drug business.industry Liver Disease Data interpretation Pharmacology and Pharmaceutical Sciences Statistical Biological Liver Pharmaceutical Preparations 030220 oncology & carcinogenesis Data Interpretation Statistical Time course Hepatic Elimination Drug business Digestive Diseases Algorithms Clearance |
| Zdroj: | Clinical pharmacology and therapeutics, vol 103, iss 3 |
| Popis: | For almost a half-century clearance concepts have been utilized in pharmacokinetics to understand the relationship between the dose administered and the time course of systemic concentrations to predict efficacy and safety, as well as how dosing should be modified in disease states. Various models of organ clearance/elimination have been proposed and tested. Surprisingly, however, the theoretical basis for the appropriate data collection to test these models has never been evaluated. Here we show that in vivo data collection limitations and the extraction ratio concept itself are only consistent with the well-stirred model of hepatic elimination. Evaluating measures of drug concentrations entering and leaving an organ will appear to best fit the well-stirred model, since driving force concentrations within the organ of elimination cannot be measured. |
| Databáze: | OpenAIRE |
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