Fexofenadine does not affect omeprazole pharmacokinetics: both are putative P-glycoprotein substrates.
An in vitro study has recently suggested that a proton pump inhibitor, omeprazole, is a modest substrate of P-glycoprotein. Several studies have shown P-glycoprotein is involved in the absorption and excretion of fexofenadine. Therefore, we examined the effect of fexofenadine on the pharmacokinetics of omeprazole. Eight healthy volunteers participated in this study. They received a single oral dose of 40 mg omeprazole before and after 60 mg fexofenadine (10 doses over 6 days). Blood samplings were performed up to 8 hr after each dosing. Plasma concentrations of omeprazole and its two metabolites were quantified with high-performance liquid chromatography. In addition, the effect of fexofenadine on P-glycoprotein function was examined by flow cytometry using rhodamine 123 and CD56-positive lymphocytes. Comparison of the pharmacokinetic parameters of omeprazole before and after fexofenadine revealed that there were no differences in peak concentration, time to peak concentration, area under the time concentration curve up to 8 hr, and elimination half-life. There were also no differences in these pharmacokinetic parameters for the two metabolites of omeprazole. Flow cytometric analysis revealed that fexofenadine did not inhibit the efflux of rhodamine 123. This study indicated that there was probably no drug interaction between omeprazole and fexofenadine, which might be due to less contribution of P-glycoprotein to omeprazole absorption, insufficient inhibitory effect of fexofenadine on P-glycoprotein, or the involvement of other transporters such as organic anion transporting polypeptides.
Takahata
Takenori
T
Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki, Japan.
Yasui-Furukori
Norio
N
Yoshiya
Gen
G
Uno
Tsukasa
T
Sugawara
Kazunobu
K
Tateishi
Tomonori
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000328:Adult; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D004347:Drug Interactions; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005838:Genotype; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics; D009853:Omeprazole / Q000097:blood / Q000493:pharmacokinetics*; D020112:Rhodamine 123; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018926:Anti-Allergic Agents; D000897:Anti-Ulcer Agents; D005456:Fluorescent Dyes; D020112:Rhodamine 123; D016593:Terfenadine; C093230:fexofenadine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole