Physiologically-Based Pharmacokinetic Modeling of Macitentan: Prediction of Drug–Drug Interactions

Clinical Pharmacokinetics

Volumn 55, Issue 3, 2016, Pages 369-380

  de Kanter, Ruben ^a   Sidharta, Patricia N ^a   Delahaye, Stéphane ^a   Gnerre, Carmela ^a   Segrestaa, Jerome ^a   Buchmann, Stephan ^a   Kohl, Christopher ^a   Treiber, Alexander ^a  

^a ACTELION PHARMACEUTICALS LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CARBAMAZEPINE; CLARITHROMYCIN; CYCLOSPORIN; DILTIAZEM; ERYTHROMYCIN; ITRACONAZOLE; KETOCONAZOLE; MACITENTAN; PHENYTOIN; RIFAMPICIN; RITONAVIR; S WARFARIN; SAQUINAVIR; SILDENAFIL; UNCLASSIFIED DRUG; VERAPAMIL; WARFARIN; ACT-132577; CYP3A4 PROTEIN, HUMAN; CYTOCHROME P450 3A; CYTOCHROME P450 3A INHIBITOR; ENDOTHELIN A RECEPTOR ANTAGONIST; ENDOTHELIN B RECEPTOR ANTAGONIST; PYRIMIDINE DERIVATIVE; SULFONAMIDE;

ACCUMULATION INDEX; ADULT; AREA UNDER THE CURVE RATIO; ARTICLE; BLOOD-TO-PLASMA RATIO; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG EFFECT; DRUG EXCRETION; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENTIATION; DRUG STABILITY; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; HUMAN TISSUE; IC50; IN VITRO STUDY; LIVER MICROSOME; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; ORAL CLEARANCE; PHYSICOCHEMICAL MODEL; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; BIOLOGICAL MODEL; BLOOD; DRUG INTERACTION; METABOLISM;

ADULT; CYCLOSPORINE; CYTOCHROME P-450 CYP3A; CYTOCHROME P-450 CYP3A INHIBITORS; DRUG INTERACTIONS; ENDOTHELIN A RECEPTOR ANTAGONISTS; ENDOTHELIN B RECEPTOR ANTAGONISTS; HUMANS; KETOCONAZOLE; MALE; MODELS, BIOLOGICAL; PYRIMIDINES; RIFAMPIN; SILDENAFIL CITRATE; SULFONAMIDES; WARFARIN;

EID: 84959081464     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.1007/s40262-015-0322-y     Document Type: Article

References (37)

1. Gatfield J, Mueller Grandjean C, Sasse T, Clozel M, Nayler O. Slow receptor dissociation kinetics differentiate macitentan from other endothelin receptor antagonists in pulmonary arterial smooth muscle cells. PloS One. 2012;7:e47662.
2. Iglarz M, Binkert C, Morrison K, Fischli W, Gatfield J, Treiber A, et al. Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist. J Pharmacol Exp Ther. 2008;327:736–45.
3. Treiber A, Aanismaa P, de Kanter R, Delahaye S, Treher M, Hess P, et al. Macitentan does not interfere with hepatic bile salt transport. J Pharmacol Exp Ther. 2014;350:130–43.
4. Galiè N, Corris PA, Frost A, Girgis RE, Granton J, Jing ZC, et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62:D60–72.
5. Cicalini S, Chinello P, Petrosillo N. HIV infection and pulmonary arterial hypertension. Expert Rev Respir Med. 2011;5:257–66.
6. Jones H, Rowland-Yeo K. Basic concepts in physiologically based pharmacokinetic modeling in drug discovery and development. CPT Pharmacomet Syst Pharmacol. 2013;2:1–12.
7. Jamei M, Dickinson GL, Rostami-Hodjegan A. A framework for assessing inter-individual variability in pharmacokinetics using virtual human populations and integrating general knowledge of physical chemistry, biology, anatomy, physiology and genetics: a tale of ‘bottom-up’ vs ‘top-down’ recognition of covariates. Drug Metab Pharmacokinet. 2009;24:53–75.
8. Jones HM, Gardner IB, Watson KJ. Modelling and PBPK simulation in drug discovery. AAPS J. 2009;11:155–66.
9. Edginton AN, Theil FP, Schmitt W, Willmann S. Whole body physiologically-based pharmacokinetic models: their use in clinical drug development. Expert Opin Drug Metab Toxicol. 2008;4:1143–52.
10. Rowland M, Peck C, Tucker G. Physiologically-based pharmacokinetics in drug development and regulatory science. Ann Rev Pharmacol Toxicol. 2011;51:45–73.
11. Huang SM, Rowland M. The role of physiologically based pharmacokinetic modeling in regulatory review. Clin Pharmacol Ther. 2012;91:542–9.
12. Sinha V, Zhao P, Huang SM, Zineh I. Physiologically based pharmacokinetic modeling: from regulatory science to regulatory policy. Clin Pharmacol Ther. 2014;95:478–80.
13. Opsumit (macitentan): summary of product characteristics. 2015. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002697/WC500160899.pdf. Accessed 21 July 2015.
14. Atsmon J, Dingemanse J, Shaikevich D, Volokhov I, Sidharta PN. Investigation of the effects of ketoconazole on the pharmacokinetics of macitentan, a novel dual endothelin receptor antagonist, in healthy subjects. Clin Pharmacokinet. 2013;52:685–92.
15. Bruderer S, Aanismaa P, Homery MC, Hausler S, Landskroner K, Sidharta PN, et al. Effect of cyclosporine and rifampin on the pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor antagonist. AAPS J. 2012;14:68–78.
16. Sidharta PN, van Giersbergen PL, Wolzt M, Dingemanse J. Investigation of mutual pharmacokinetic interactions between macitentan, a novel endothelin receptor antagonist, and sildenafil in healthy subjects. Br J Clin Pharmacol. 2014;78:1035–42.
17. Sidharta PN, Dietrich H, Dingemanse J. Investigation of the effect of macitentan on the pharmacokinetics and pharmacodynamics of warfarin in healthy male subjects. Clin Drug Investig. 2014;34:545–52.
18. van Giersbergen PL, Gnerre C, Treiber A, Dingemanse J, Meyer UA. Bosentan, a dual endothelin receptor antagonist, activates the pregnane X nuclear receptor. Eur J Pharmacol. 2002;450:115–21.
19. Proctor N, Tucker G, Rostami-Hodjegan A. Predicting drug clearance from recombinantly expressed CYPs: intersystem extrapolation factors. Xenobiotica. 2004;34:151–78.
20. Bruderer S, Hopfgartner G, Seiberling M, Wank J, Sidharta PN, Treiber A, et al. Absorption, distribution, metabolism, and excretion of macitentan, a dual endothelin receptor antagonist, in humans. Xenobiotica. 2012;42:901–10.
21. Center for Drug Evaluation and Research. Application number 204410Orig1s000. Clinical pharmacology and biopharmaceutics review(s). 2013. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000ClinPharmR.pdf. Accessed 21 July 2015.
22. Yang J, Jamei M, Yeo KR, Tucker GT, Rostami-Hodjegan A. Prediction of intestinal first-pass drug metabolism. Curr Drug Metab. 2007;8:676–84.
23. Pang KS, Chow EC. Commentary: theoretical predictions of flow effects on intestinal and systemic availability in physiologically based pharmacokinetic intestine models: the traditional model, segregated flow model, and QGut model. Drug Metab Dispos. 2012;40:1869–77.
24. Rodgers T, Rowland M. Physiologically based pharmacokinetic modelling 2: predicting the tissue distribution of acids, very weak bases, neutrals and zwitterions. J Pharm Sci. 2006;95:1238–57.
25. Rowland M, Tozer T. Metabolite kinetics, Chap 21. In: Clinical pharmacokinetics: concepts and applications. 3rd ed. Media, PA: Lippincott Williams & Wilkins; 1994. p. 372.
26. Sidharta PN, van Giersbergen PL, Dingemanse J. Safety, tolerability, pharmacokinetics, and pharmacodynamics of macitentan, an endothelin receptor antagonist, in an ascending multiple-dose study in healthy subjects. J Clin Pharmacol. 2013;53:1131–8.
27. Wagner C, Pan Y, Hsu V, Grillo JA, Zhang L, Reynolds KS, et al. Predicting the effect of cytochrome P450 inhibitors on substrate drugs: analysis of physiologically based pharmacokinetic modeling submissions to the US Food and Drug Administration. Clin Pharmacokinet. 2015;54:117–27.
28. Darwich AS, Neuhoff S, Jamei M, Rostami-Hodjegan A. Interplay of metabolism and transport in determining oral drug absorption and gut wall metabolism: a simulation assessment using the “Advanced Dissolution, Absorption, Metabolism (ADAM)” model. Curr Drug Metab. 2010;11:716–29.
29. Zisowsky J, Sidharta P, Krause A, Dingemanse J. Pharmacokinetic/pharmacodynamic analyses in SERAPHIN, a randomized, controlled study of macitentan in patients with pulmonary arterial hypertension. Clin Pharmacol Drug Dev. 2013;2:S29.
30. Zientek MA, Youdim K. Reaction phenotyping: advances in the experimental strategies used to characterize the contribution of drug-metabolizing enzymes. Drug Metab Dispos. 2015;43:163–81.
31. Tsamandouras N, Rostami-Hodjegan A, Aarons L. Combining the “bottom-up” and “top-down” approaches in pharmacokinetic modelling: fitting PBPK models to observed clinical data. Br J Clin Pharmacol. 2013;79:48–55.
32. Zhao P, Ragueneau-Majlessi I, Zhang L, Strong JM, Reynolds KS, Levy RH, et al. Quantitative evaluation of pharmacokinetic inhibition of CYP3A substrates by ketoconazole: a simulation study. J Clin Pharmacol. 2009;49:351–9.
33. Opsumit (macitentan): US prescribing information. 2015. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204410s003lbl.pdf. Accessed 21 July 2015.
34. Australian Public Assessment Report for macitentan. 2014. http://www.tga.gov.au/file/5941/download. Accessed 21 July 2015.
35. Baxter JG, Brass C, Schentag JJ, Slaughter RL. Pharmacokinetics of ketoconazole administered intravenously to dogs and orally as tablet and solution to humans and dogs. J Pharm Sci. 1986;75:443–7.
36. Kummer O, Haschke M, Hammann F, Bodmer M, Bruderer S, Regnault Y, et al. Comparison of the dissolution and pharmacokinetic profiles of two galenical formulations of the endothelin receptor antagonist macitentan. Eur J Pharm Sci. 2009;38:384–8.
37. Bruderer S, Marjason J, Sidharta PN, Dingemanse J. Pharmacokinetics of macitentan in caucasian and Japanese subjects: the influence of ethnicity and sex. Pharmacology. 2013;91:331–8.