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Comparison of the dissolution and pharmacokinetic profiles of two galenical formulations of the endothelin receptor antagonist macitentan

Kummer, Oliver and Haschke, Manuel and Hammann, Felix and Bodmer, Michael and Bruderer, Shirin and Regnault, Yann and Dingemanse, Jasper and Krähenbühl, Stephan. (2009) Comparison of the dissolution and pharmacokinetic profiles of two galenical formulations of the endothelin receptor antagonist macitentan. European journal of pharmaceutical sciences, Vol. 38, H. 4. pp. 384-388.

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Official URL: http://edoc.unibas.ch/dok/A5261864

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Abstract

Macitentan (ACT-064992) is an orally active endothelin receptor antagonist. We first compared the in vitro dissolution characteristics of uncoated and film-coated tablets with hard gelatin capsules containing 10mg ACT-064992. Subsequently, we compared the oral pharmacokinetics of ACT-064992 and its active metabolite ACT-132577 of the coated tablet and the gelatin capsule formulation in 11 male volunteers. The dissolution profile showed a rapid disintegration of all formulations with <90% dissolution of ACT-064992 within 45 min. The pharmacokinetics of ACT-064992 and its metabolite ACT-132577 were comparable for the two formulations. ACT-064992 revealed a slow absorption (median t(max) 8h) and a terminal half-life of approximately 13 h. Bioequivalence criteria were met for AUC(0-t) and AUC(0-infinity). Mean C(max) was 19% lower after ingestion of the tablet compared to capsules with its lower 90% confidence limit below the accepted bioequivalence range. The pharmacokinetics of the metabolite ACT-132577, characterized by a t(max) of approximately 48 h and a terminal half-life of approximately 45 h, was not different between the two formulations. We conclude that the absorption profile of the tablet differs from the capsule in peak but not in total exposure, which is not expected to be of clinical significance.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmakologie (Krähenbühl)
UniBasel Contributors:Krähenbühl, Stephan
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:0928-0987
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2013 11:11
Deposited On:22 Mar 2012 13:38

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