The effect of AST-120 on the single-dose pharmacokinetics of metoprolol extended-release tablets in healthy subjects
-
Shinsuke Inoue
,
Miho Shimizu
Abstract
Background: This was a randomized, open-label, three-way crossover study to assess the effects of AST-120 (an orally administered spherical carbon adsorbent acting in the gastrointestinal tract without systemic circulation) on the single-dose pharmacokinetics of metoprolol in an extended-release formulation (metoprolol ER) in healthy volunteers.
Methods: A total of 34 subjects were singly administered metoprolol ER alone (A), and metoprolol ER in combination with AST-120 simultaneously (B) and 1 h later (C).
Results: The total exposure was more significantly reduced in both treatments B and C than that in treatment A; the geometric mean ratios of area under the curve extrapolated to infinity (AUC0–∞) for B/A and C/A were reduced by approximately 30% in both treatments B and C. Maximum observed plasma concentration (Cmax) of metoprolol in treatment B significantly decreased, whereas Cmax in treatment C was slightly decreased. AST-120 treatment was unlikely to affect apparent first-order terminal elimination half-life (T1/2) of metoprolol significantly. Reduction in heart rate and blood pressure readings were similar across the treatment periods. Coadministration of AST-120 and metoprolol ER was safe and was well tolerated.
Conclusions: Because AST-120 reduced gastrointestinal absorption of metoprolol ER, careful monitoring of heart rate and blood pressure is recommended in coadministration of AST-120 with metoprolol ER.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.
Research funding: None declared.
Employment or leadership: The authors report employment with Mitsubishi Tanabe Pharma Corporation.
Honorarium: None declared.
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Artikel in diesem Heft
- Frontmatter
- Editorial
- Importance of ABC transporters in different tissues
- Review
- Pharmacogenetic potential biomarkers for carbamazepine adverse drug reactions and clinical response
- Reviews in Population Pharmacogenomics
- The pharmacogenetics of drug metabolizing enzymes in the Lebanese population
- Original Articles
- Characterization of ABC transporters in human skin
- Binary and ternary combinations of anti-HIV protease inhibitors: effect on gene expression and functional activity of CYP3A4 and efflux transporters
- Raloxifene pharmacodynamics is influenced by genetic variants in the RANKL/RANK/OPG system and in the Wnt signaling pathway
- The effect of AST-120 on the single-dose pharmacokinetics of metoprolol extended-release tablets in healthy subjects
- Case Report
- Liver enzyme abnormalities during antipsychotic treatment: a case report of risperidone-associated hepatotoxicity
