Permeability classification of representative fluoroquinolones by a cell culture method
Journal Title: The AAPS Journal - Year 2004, Vol 6, Issue 2
Abstract
This study was undertaken to categorize representative fluoroquinolone drug substance permeability based on the methods outlined in the Food and Drug Administration's biopharmaceutic classification system (BCS) Guidance for Industry. The permeability of ciprofloxacin, levofloxacin, lomefloxacin, and ofloxacin was measured in an in vitro Caco-2 assay with previously demonstrated method suitability. The permeability class and efflux potential were ascertained by comparing test drug results with standard compounds (metoprolol, atenolol, labetalol, and rhodamine-123). All 4 quinolones drugs demonstrated concentration-dependent permeability, indicating active drug transport. In comparing absorptive versus secretive in vitro transport, the tested fluoroquinolones were found to be subject to efflux in varying degrees (ciprofloxacin > lomefloxacin > rhodamine 123 > levofloxacin > ofloxacin). Based on comparison to labetalol, the high permeability internal standard, ciprofloxacin was classified as a low permeability drug, whereas lomefloxacin, levofloxacin, and ofloxacin were classified as high permeability drugs. The in vitro permeability results matched human in vivo data based on absolute bioavailabilities. This laboratory exercise demonstrated the applicability of an in vitro permeability method for classifying drugs as outlined in the BCS Guidance.
Authors and Affiliations
Donna A. Volpe
Keywords
Related Articles
- EP ID EP681948
- DOI 10.1208/ps060213
- Views 81
- Downloads 0
Further advances in the synthesis of endocannabinoid-related ligands
Recent advances in the synthesis of endocannabinoid-related ligands for the period 2001–2004 are covered in this review. During this period the first solid phase synthesis of anandamide (AEA) analogs was develope...
Statistical Comparison of Dissolution Profiles to Predict the Bioequivalence of Extended Release Formulations
The online version of this article (doi:10.1208/s12248-014-9615-6) contains supplementary material, which is available to authorized users.
Causes and consequences of methamphetamine and MDMA toxicity
Methamphetamine (METH) and its derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) are 2 substituted amphetamines with very high abuse liability in the United States. These amphetamine-like stimulants have been...
Mixed Effects Modeling Using Stochastic Differential Equations: Illustrated by Pharmacokinetic Data of Nicotinic Acid in Obese Zucker Rats
Inclusion of stochastic differential equations in mixed effects models provides means to quantify and distinguish three sources of variability in data. In addition to the two commonly encountered sources, measurement err...
Assessment and Reporting of the Clinical Immunogenicity of Therapeutic Proteins and Peptides—Harmonized Terminology and Tactical Recommendations
Immunogenicity is a significant concern for biologic drugs as it can affect both safety and efficacy. To date, the descriptions of product immunogenicity have varied not only due to different degrees of understanding of...