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Probenecid, but Not Cystic Fibrosis, Alters the Total and Renal Clearance of Fexofenadine
Author(s) -
Liu Shanshan,
Beringer Paul M.,
Hidayat Levita,
Rao Adupa P.,
Louie Stan,
Burckart Gilbert J.,
Shapiro Bertrand
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270008319707
Subject(s) - fexofenadine , cystic fibrosis , probenecid , pharmacology , medicine , pharmacokinetics , cmax , gastroenterology , terfenadine , crossover study , pathology , alternative medicine , placebo
This study aims to evaluate renal P‐glycoprotein (P‐gp) activity in patients with cystic fibrosis. P‐gp efflux activity in peripheral T cells was measured by flow cytometry in 10 cystic fibrosis and 15 healthy volunteers. Eight cystic fibrosis patients and 8 healthy volunteers were recruited into a crossover pharmacokinetic study in which participants received 180 mg fexofenadine with or without 1 g probenecid twice a day. Genotyping was performed for ABCB 1 C1236T, G2677T, and C3435T. P‐gp efflux activity in peripheral T cells was not significantly different between cystic fibrosis patients and healthy volunteers. No difference in fexofenadine pharmacokinetic parameters was observed between cystic fibrosis patients and healthy volunteers when fexofenadine was administered with or without probenecid. Coadministration of probenecid significantly increased fexofenadine AUC and decreased the cumulative urinary excretion, total body clearance, and renal clearance. ABCB 1 3435 C/T carriers showed increased basal P‐gp activity in CD4+ and CD8+ T cells, increased R123‐induced efflux activity in CD4+ T cell, and decreased fexofenadine AUC. Fexofenadine disposition and P‐gp efflux activity in peripheral T cells was similar between cystic fibrosis patients and healthy volunteers. Probenecid administration significantly reduced the total body and renal clearance of fexofenadine. ABCB 1 3435 C/T was associated with an elevated efflux activity compared with C/C subjects.