Stereoselective renal tubular secretion of levocetirizine and dextrocetirizine, the two enantiomers of the H1-antihistamine cetirizine.
Fundam Clin Pharmacol
; 22(1): 19-23, 2008 Feb.
Article
em En
| MEDLINE
| ID: mdl-18005357
ABSTRACT
Competition for uptake and/or efflux transporters can be responsible for drug interactions. Cetirizine is mainly eliminated unchanged in urine through both glomerular filtration and tubular secretion. The aim of this study was to investigate whether the eutomer, levocetirizine, and the distomer, dextrocetirizine, have a similar tubular secretion. The renal clearance associated with tubular secretion was calculated from the renal clearance of levocetirizine and dextrocetirizine obtained in a study in healthy volunteers. The values of the unbound fraction in plasma were obtained in an in vitro study of the binding of (14)C-cetirizine and (14)C-levocetirizine to human plasma proteins using equilibrium dialysis and chiral high-performance liquid chromatography (HPLC) with on-line liquid scintillation counting. The unbound fraction was 0.074 for levocetirizine and 0.141 for dextrocetirizine. The tubular secretion of dextrocetirizine (44.5 mL/min) is higher than that of levocetirizine (23.1 mL/min), which may have consequences for drug interactions at the renal level. The higher tubular secretion for dextrocetirizine may be due to the higher free fraction available for secretion or to a higher affinity for (a) renal transporter(s) mediating the secretion pathway.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Cetirizina
/
Antagonistas não Sedativos dos Receptores H1 da Histamina
/
Túbulos Renais
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Fundam Clin Pharmacol
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
França