Fluoroquinolone disposition: identification of the contribution of renal secretory and reabsorptive drug transporters.
Expert Opin Drug Metab Toxicol
; 8(5): 553-69, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22435536
ABSTRACT
INTRODUCTION:
Fluoroquinolones (FQs) exist as charged molecules in blood and urine making their absorption, distribution, and elimination likely to be influenced by active transport mechanisms. Greater understanding of in vivo FQ clearance mechanisms should help improve the predictability of drug-drug interactions, enhance the clinical safety and efficacy, and aid future novel drug design strategies. AREAS COVERED The authors present an overview of FQ development and associated drug-drug interactions, followed by systematic quantitative review of the physicochemical and in vivo pharmacokinetic properties for 15 representative FQs using historical clinical literature. These results were correlated with in vitro studies implicating drug transporters in FQ clearance to link clinical and in vitro evidence supporting the contribution of drug transport mechanisms to FQ disposition. Specific transporters likely to handle FQs in human renal proximal tubule cells are also identified. EXPERT OPINION Renal handling, that is, tubular secretion and reabsorption, appears to be the main determinant of FQ plasma half-life, clinical duration of action, and drug-drug interactions. Due to their zwitterionic nature, FQs are likely to interact with organic anion and cation transporters within the solute carrier (SLC) superfamily, including OAT1, OAT3, OCT2, OCTN1, OCTN2, MATE1, and MATE2. The ATP-binding cassette (ABC) transporters MDR1, MRP2, MRP4, and BCRP also may interact with FQs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fluoroquinolonas
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Túbulos Renais Proximais
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
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Systematic_reviews
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article