Relative bioavailability of a newly developed pediatric formulation of bosentan vs. the adult formulation

International Journal of Clinical Pharmacology and Therapeutics

Volumn 51, Issue 6, 2013, Pages 529-536

  Gutierrez, Marcelo M ^a   Nicolas, Laurent B ^a   Donazzolo, Yves ^b   Dingemanse, Jasper ^a  

^a ACTELION PHARMACEUTICALS LTD   (Switzerland)

^b Eurofins Medinet Inc   (Germany)

Author keywords

Adult formulation; Bosentan; Orphan indication; Pediatric formulation; Pharmacokinetics; Pulmonary arterial hypertension

Indexed keywords

BOSENTAN; RO 47 8634; RO 48 5033; RO 64 1056; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; CLINICAL ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DRUG BIOAVAILABILITY; DRUG DOSE COMPARISON; DRUG ELIMINATION; DRUG FORMULATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; HUMAN; MALE; MAXIMUM PLASMA CONCENTRATION; PHARMACODYNAMICS; PULMONARY HYPERTENSION; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE;

ADULT; ANTIHYPERTENSIVE AGENTS; BIOLOGICAL AVAILABILITY; CHEMISTRY, PHARMACEUTICAL; CROSS-OVER STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; HUMANS; HYPERTENSION, PULMONARY; MALE; MIDDLE AGED; PREDICTIVE VALUE OF TESTS; RECEPTORS, ENDOTHELIN; SULFONAMIDES; TABLETS;

EID: 84878790344     PISSN: 09461965     EISSN: None     Source Type: Journal    
DOI: 10.5414/CP201806     Document Type: Article

References (19)

1. Rubin LJ. Primary pulmonary hypertension. N Engl J Med. 1997; 336: 111-117. doi:10.1056/NEJM199701093360207 PubMed (Pubitemid 27020889)
2. Farber HW, Loscalzo J. Pulmonary arterial hypertension. N Engl J Med. 2004; 351: 1655-1665. doi:10.1056/NEJMra035488 PubMed
3. Anderson JR, Nawarskas JJ. Pharmacotherapeutic management of pulmonary arterial hypertension. Cardiol Rev. 2010; 18: 148-162. doi:10.1097/CRD. 0b013e3181d4e921 PubMed
4. Channick RN, Simonneau G, Sitbon O, Robbins IM, Frost A, Tapson VF, Badesch DB, Roux S, Rainisio M, Bodin F, Rubin LJ. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001; 358: 1119-1123. doi:10.1016/S0140-6736(01)06250-X PubMed (Pubitemid 32971843)
5. Beghetti M. Bosentan in pediatric patients with pulmonary arterial hypertension. Curr Vasc Pharmacol. 2009; 7: 225-233. doi:10.2174/ 157016109787455653 PubMed
6. Rosenzweig EB, Ivy DD, Widlitz A, Doran A, Claussen LR, Yung D, Abman SH, Morganti A, Nguyen N, Barst RJ. Effects of long-term bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol. 2005; 46: 697-704. doi:10.1016/j.jacc.2005.01.066 PubMed (Pubitemid 41132700)
7. Dingemanse J, van Giersbergen PLM. Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. Clin Pharmacokinet. 2004; 43: 1089-1115. doi:10.2165/00003088-200443150-00003 PubMed (Pubitemid 40013178)
8. Weber C, Gasser R, Hopfgartner G. Absorption, excretion, and metabolism of the endothelin receptor antagonist bosentan in healthy male subjects. Drug Metab Dispos. 1999; 27: 810-815. PubMed (Pubitemid 29297779)
9. Barst RJ, Ivy D, Dingemanse J, Widlitz A, Schmitt K, Doran A, Bingaman D, Nguyen N, Gaitonde M, van Giersbergen PL. Pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. Clin Pharmacol Ther. 2003; 73: 372-382. doi:10.1016/S0009-9236(03)00005-5 PubMed (Pubitemid 36403597)
10. Beghetti M, Haworth SG, Bonnet D, Barst RJ, Acar P, Fraisse A, Ivy DD, Jais X, Schulze-Neick I, Galiè N, Morganti A, Dingemanse J, Kusic-Pajic A, Berger RM. Pharmacokinetic and clinical profile of a novel formulation of bosentan in children with pulmonary arterial hypertension: the FUTURE-1 study. Br J Clin Pharmacol. 2009; 68: 948-955. doi:10.1111/j.1365-2125.2009.03532.x PubMed
11. Dingemanse J, Bodin F, Weidekamm E, Kutz K, van Giersbergen P. Influence of food intake and formulation on the pharmacokinetics and metabolism of bosentan, a dual endothelin receptor antagonist. J Clin Pharmacol. 2002; 42: 283-289. doi:10.1177/00912700222011300 PubMed (Pubitemid 34163474)
12. Dell D, Lausecker B, Hopfgartner G, Giersbergen PLM, Dingemanse J. Evolving bioanalytical methods for the cardiovascular drug bosentan. Chromatographia. 2002; 55 (Suppl): S115-S119. doi:10.1007/BF02493366 (Pubitemid 34548120)
13. Lausecker B, Hess B, Fischer G, Mueller M, Hopfgartner G. Simultaneous determination of bosentan and its three major metabolites in various biological matrices and species using narrow bore liquid chromatography with ion spray tandem mass spectrometric detection. J Chromatogr B Biomed Sci Appl. 2000; 749: 67-83. doi:10.1016/S0378-4347(00)00386-8 PubMed
14. Guidance for Industry. Bioanalytical method validation . Food and Drug Administration, May 2001.
15. Pirie WR, Hollander M. Notes on a Tukey test for ordered alternatives. Ann Inst Stat Math. 1975; 27: 521-523. doi:10.1007/BF02504669
16. van Giersbergen PL, Dingemanse J. Comparative investigation of the pharmacokinetics of bosentan in Caucasian and Japanese healthy subjects. J Clin Pharmacol. 2005; 45: 42-47. doi:10.1177/0091270004270833 PubMed
17. van Giersbergen PL, Halabi A, Dingemanse J. Single- and multiple-dose pharmacokinetics of bosentan and its interaction with ketoconazole. Br J Clin Pharmacol. 2002; 53: 589-595. doi:10.1046/j.1365-2125.2002.01608.x PubMed (Pubitemid 34621784)
18. Weber C, Schmitt R, Birnboeck H, Hopfgartner G, van Marle SP, Peeters PA, Jonkman JH, Jones CR. Pharmacokinetics and pharmacodynamics of the endothelin-receptor antagonist bosentan in healthy human subjects. Clin Pharmacol Ther. 1996; 60: 124-137. doi:10.1016/S0009-9236(96)90127-7 PubMed (Pubitemid 26348226)
19. Summary of product characteristics. Tracleer. Actelion Registration Ltd. December 2011.