Macitentan: Entry-into-humans study with a new endothelin receptor antagonist

European Journal of Clinical Pharmacology

Volumn 67, Issue 10, 2011, Pages 977-984

  Sidharta, Patricia N ^a   Van Giersbergen, Paul L M ^a   Halabi, Atef ^b   Dingemanse, Jasper ^a  

^a ACTELION PHARMACEUTICALS LTD   (Switzerland)

^b Clinical Research Services Kiel GmbH   (Germany)

Author keywords

Endothelin receptor antagonist; Healthy subjects; Pharmacodynamics; Pharmacokinetics; Tolerability

Indexed keywords

ACT 132577; BILE SALT; DRUG METABOLITE; ENDOTHELIN 1; MACITENTAN; PLACEBO; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; AREA UNDER THE CURVE; ARTICLE; BACKACHE; CLINICAL LABORATORY; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG URINE LEVEL; ELECTROCARDIOGRAPHY; HOT FLUSH; HUMAN; HUMAN EXPERIMENT; LEUKOCYTOSIS; LIVER DYSFUNCTION; MALE; MAXIMUM PLASMA CONCENTRATION; NAUSEA AND VOMITING; NECK PAIN; NORMAL HUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINITIS; RHINOPHARYNGITIS; SIDE EFFECT; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; VITAL SIGN;

ADULT; BILE ACIDS AND SALTS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG TOLERANCE; ENDOTHELIN-1; HUMANS; MALE; MIDDLE AGED; PLACEBOS; PYRIMIDINES; RECEPTORS, ENDOTHELIN; SULFONAMIDES; YOUNG ADULT;

EID: 80054771944     PISSN: 00316970     EISSN: 14321041     Source Type: Journal    
DOI: 10.1007/s00228-011-1043-2     Document Type: Article

References (21)

1. M Yanagisawa H Kurihara S Kimura Y Tomobe M Kobayashi Y Mitsui Y Yazaki K Goto T Masaki 1988 A novel potent vasoconstrictor peptide produced by vascular endothelial cells Nature 332 411 415 2451132 10.1038/332411a0 1:CAS:528:DyaL1cXlsVaks78%3D (Pubitemid 18090241)
2. NS Kirkby PW Hadoke AJ Bagnall DJ Webb 2008 The endothelin system as a therapeutic target in cardiovascular disease: great expectations or bleak house? Br J Pharmacol 153 1105 1119 17965745 10.1038/sj.bjp.0707516 1:CAS:528:DC%2BD1cXjtlelurc%3D (Pubitemid 351415492)
3. M Barton M Yanagisawa 2008 Endothelin: 20 years from discovery to therapy Can J Physiol Pharmacol 86 485 498 18758495 10.1139/Y08-059 1:CAS:528:DC%2BD1cXhtVGnurfM
4. TK Trow DB Taichman 2009 Endothelin receptor blockade in the management of pulmonary arterial hypertension: selective and dual antagonism Respir Med 103 951 962 19304472 10.1016/j.rmed.2009.02.016
5. LC Price LS Howard 2008 Endothelin receptor antagonists for pulmonary arterial hypertension: rationale and place in therapy Am J Cardiovasc Drugs 8 171 185 18533738 10.2165/00129784-200808030-00004 1:CAS:528:DC%2BD1cXptFyisr4%3D (Pubitemid 351812270)
6. MA Weber H Black G Bakris H Krum S Linas R Weiss JV Linseman BL Wiens MS Warren LH Lindholm 2009 A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomised, double-blind, placebo-controlled trial Lancet 374 1423 1431 19748665 10.1016/S0140-6736(09)61500-2 1:CAS:528:DC%2BD1MXhtlSru7jK
7. RM Green F Hoda KL Ward 2000 Molecular cloning and characterization of the murine bile salt export pump Gene 241 117 123 10607905 10.1016/S0378- 1119(99)00460-6 1:CAS:528:DyaK1MXotVGltbo%3D
8. K Fattinger C Funk M Pantze C Weber J Reichen B Stieger PJ Meier 2001 The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions Clin Pharmacol Ther 69 223 231 11309550 10.1067/mcp.2001.114667 1:CAS:528:DC%2BD3MXjvVelsbo%3D (Pubitemid 32382504)
9. AP Comellas A Briva LA Dada ML Butti HE Trejo C Yshii ZS Azzam J Litvan J Chen E Lecuona LM Pesce M Yanagisawa JI Sznajder 2009 Endothelin-1 impairs alveolar epithelial function via endothelial ETB receptor Am J Respir Crit Care Med 179 113 122 18948426 10.1164/rccm.200804-540OC 1:CAS:528: DC%2BD1MXitFCktrg%3D
10. M Iglarz C Binkert K Morrison W Fischli J Gatfield A Treiber T Weller MH Bolli C Boss S Buchmann B Capeleto P Hess C Qiu M Clozel 2008 Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist J Pharmacol Exp Ther 327 736 745 18780830 10.1124/jpet.108.142976 1:CAS:528:DC%2BD1cXhsVCjtLvO
11. J Dingemanse F Bodin E Weidekamm K Kutz P van Giersbergen 2002 Influence of food intake and formulation on the pharmacokinetics and metabolism of bosentan, a dual endothelin receptor antagonist J Clin Pharmacol 42 283 289 11865964 10.1177/00912700222011300 1:CAS:528:DC%2BD38XitVKnsLo%3D (Pubitemid 34163474)
12. K Gough M Hutchison O Keene 1995 Assessment of dose proportionality: report from the statisticians in the pharmaceutical industry/pharmacokinetics UK joint working party Drug Inf J 29 1039 1048
13. J Dingemanse M Clozel PLM van Giersbergen 2002 Pharmacokinetics and pharmacodynamics of tezosentan, an intravenous dual endothelin receptor antagonist, following chronic infusion in healthy subjects Br J Clin Pharmacol 53 355 362 11966665 10.1046/j.1365-2125.2002.01158.x 1:CAS:528: DC%2BD38Xjs1eitrY%3D (Pubitemid 34415584)
14. PLM Van Giersbergen J Dingemanse 2007 Tolerability, pharmacokinetics, and pharmacodynamics of clazosentan, a parenteral endothelin receptor antagonist Eur J Clin Pharmacol 63 151 158 16636870 10.1007/s00228-006-0117-z 1:CAS:528:DC%2BD2sXnsFyktA%3D%3D (Pubitemid 46147056)
15. C Weber R Schmitt H Birnboeck G Hopfgartner SP van Marle PAM Peeters JH Jonkman CR Jones 1996 Pharmacokinetics and pharmacodynamics of the endothelin-receptor antagonist bosentan in healthy human subjects Clin Pharmacol Ther 60 124 137 8823230 10.1016/S0009-9236(96)90127-7 1:CAS:528: DyaK28XmsFSktrg%3D (Pubitemid 26348226)
16. P Rosenzweig N Miget S Brohier 1999 Transaminase elevation on placebo during Phase I trials: prevalence and significance Br J Clin Pharmacol 48 19 23 10383555 10.1046/j.1365-2125.1999.00952.x 1:STN:280:DyaK1MzhsFaqsw%3D%3D (Pubitemid 29296658)
17. JC Hartman K Brouwer A Mandagere L Melvin R Gorczynski 2010 Evaluation of the endothelin receptor antagonists ambrisentan, darusentan, bosentan, and sitaxsentan as substrates and inhibitors of hepatobiliary transporters in sandwich-cultured human hepatocytes Can J Physiol Pharmacol 88 682 691 20628435 10.1139/Y10-060 1:CAS:528:DC%2BC3cXpt1aru78%3D
18. M Humbert ES Segal DG Kiely J Carlsen B Schwierin MM Hoeper 2007 Results of European post-marketing surveillance of bosentan in pulmonary hypertension Eur Respir J 30 338 344 17504794 10.1183/09031936.00138706 1:CAS:528: DC%2BD2sXpvFCgs7k%3D (Pubitemid 47194187)
19. B receptors in rats Biochem Biophys Res Commun 199 1461 1465 8147891 10.1006/bbrc.1994.1395 1:CAS:528:DyaK2cXitlOjsLo%3D
20. J Dupuis MM Hoeper 2008 Endothelin receptor antagonists in pulmonary arterial hypertension Eur Respir J 31 407 415 18238950 10.1183/09031936.00078207 1:CAS:528:DC%2BD1cXit12gsrw%3D
21. CF Opitz R Ewert W Kirch D Pittrow 2008 Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter? Eur Heart J 29 1936 1948 18562303 10.1093/eurheartj/ehn234 1:CAS:528:DC%2BD1cXhtFajsbfM