Effects of rifampicin (Rifampin) on the pharmacokinetics and safety of ambrisentan in healthy subjects: A single-sequence, open-label study

Clinical Drug Investigation

Volumn 30, Issue 12, 2010, Pages 875-885

  Harrison, Brooke ^a   Magee, Mindy H ^b   Mandagere, Arun ^a   Walker, Gennyne ^a   Dufton, Christopher ^a   Henderson, Linda S ^b   Boinpally, Ramesh ^a  

^a GILEAD SCIENCES   (United States)

^b GLAXOSMITHKLINE   (United States)

Author keywords

Ambrisentan, pharmacokinetics; Endothelin receptor antagonists, pharmacokinetics; Pulmonary hypertension; Research and development; Rifampicin, pharmacokinetics

Indexed keywords

4 HYDROXYMETHYL AMBRISENTAN; ALANINE AMINOTRANSFERASE; AMBRISENTAN; CYTOCHROME P450 3A4; DRUG METABOLITE; RIFAMPICIN; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG EFFECT; DRUG EXPOSURE; DRUG METABOLISM; DRUG MONITORING; DRUG POTENCY; DRUG SAFETY; DRUG TOLERABILITY; ELECTROCARDIOGRAM; ENZYME INDUCTION; FEMALE; FOLLOW UP; HEADACHE; HUMAN; MALE; MAXIMUM PLASMA CONCENTRATION; MONOTHERAPY; NORMAL HUMAN; OPEN STUDY; OUTCOME ASSESSMENT; PRIORITY JOURNAL; SIDE EFFECT; STEADY STATE; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT DURATION; VITAL SIGN;

ADMINISTRATION, ORAL; ADULT; ANTI-BACTERIAL AGENTS; ANTIHYPERTENSIVE AGENTS; BIOTRANSFORMATION; CYTOCHROME P-450 CYP3A; DRUG INTERACTIONS; ENZYME INDUCTION; FEMALE; FLORIDA; HUMANS; MALE; MIDDLE AGED; ORGANIC ANION TRANSPORTERS; PHENYLPROPIONATES; PYRIDAZINES; RECEPTOR, ENDOTHELIN A; RIFAMPIN;

EID: 77957787232     PISSN: 11732563     EISSN: 11791918     Source Type: Journal    
DOI: 10.2165/11539110-000000000-00000     Document Type: Article

References (23)

1. Rubin LJ. Primary pulmonary hypertension. Chest 1993; 104: 236-50
2. Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hyperten-sion. J Am Coll Cardiol 2004; 43: 13S-24S
3. Galie N, Olschewski H, Oudiz R, et al. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multi-center, Efficacy (ARIES) study 1 and 2. Circulation 2008; 117: 3010-9
4. Galie N, Badesch D, Oudiz R, et al. Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2005; 46: 529-35
5. Gilead Sciences Inc. Letairis (ambrisentan) tablets for oral use. United States Food and Drug Administration drug product label 2009 [online]. Available from URL: http://www.letairis.com/patients/fpi.asp [Accessed 2010 Aug 1]
6. Oudiz R, Galie N, Olschewski H, et al. Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension. J Am Coll Cardiol 2009; 54: 1971-81
7. Actelion Pharmaceuticals Ltd. 2009. Tracleer (bosentan) tablets. United States Food and Drug Administration drug product label [online]. Available from URL: http://www.tracleer.com/Content/Pdf/Tracleer-Full-Prescribing-Information- Aug09.pdf[Accessed 2010 Aug1]
8. Girgis R. Sitaxsentan in the treatment ofpulmonary arterial hypertension: a clinical update. J Resp Dis 2007; 28: S1
9. Gilead Sciences Inc. Food and Drug Administration [pharmacology review (part 1)] for original new drug application 22-081 [online]. Available from http://www.accessdata. fda.gov/drugsatfda-docs/nda/2007/022081s000-PharmR-P1. pdf[Accessed 2009 Oct 1]
10. Spence R, Harrison B, Mandagere A, et al. No clinical relevant pharmacokinetic interaction between ambrisentan and tadalafil. J Pharm Sciences 2009; 98: 4962-74
11. Richards DB, Walker GA, Mandagere A, et al. Effect of ketoconazole on the pharmacokinetic profile of am-brisentan. J Clin Pharmacol 2009; 49: 719-24
12. Niemi M, Backman JT, Fromm MF, et al. Pharmacokinetic interactions with rifampicin: clinical relevance. Clin Pharma-cokinet 2003; 42: 819-50
13. Vavricka SR, Van MJ, Ha HR, et al. Interactions of rifamycin SV and rifampicin with organic anion uptake sys-tems of human liver. Hepatology 2002; 36: 164-72
14. Treiber A, Schneiter R, Hausler S, et al. Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interac-tions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos 2007; 35: 1400-7
15. Hirano M, Maeda K, Shitara Y, et al. Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos 2006; 34: 1229-36
16. Lau YY, Okochi H, Huang Y, et al. Pharmacokinetics of atorvastatin and its hydroxy metabolites in rats and the effects ofconcomitant rifampicin single doses: relevance offirst-pass effect from hepatic uptake transporters, and intestinal and hepatic metabolism. Drug Metab Dispos 2006; 34: 1175-81
17. Xiong H, Carr RA, Locke CS, et al. Dual effects of rifampin on the pharmacokinetics of atrasentan. J Clin Pharmacol 2007; 47: 423-9
18. Van Giersbergen PL, Treiber A, Schneiter R, et al. Inhibitory and inductive effects of rifampin on the pharmaco-kinetics of bosentan in healthy subjects. Clin Pharmacol Ther 2007; 81: 414-9
19. Zheng HX, Huang AH, Frassetto LA, et al. Elucidating rifampin's inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers: unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its primary metabo-lite. Clin Pharmacol Ther 2009; 85: 78-85
20. FDA 2003. Guidance for industry: bioavailability and bioequivalence studies for orally administered drug products: general considerations [online]. Available from URL: www. fda.gov/./Drugs/GuidanceComplianceRegulatoryInforma tion/Guidances/ucm070124.pdf[Accessed2010 Sep 1]
21. Spence R, Mandagere A, Dufton C, et al. Pharmacokinetics and safety of ambrisentan in combination with sildenafil in healthy volunteers. J Clin Pharmacol 2008; 48: 1451-9
22. Loos U, Musch E, Jensen JC, et al. Pharmacokinetics oforal and intravenous rifampicin during chronic administration. KlinWochenschr 1985; 63: 1205-11
23. Walker G, Mandagere A, Dufton C, et al. The pharmacokinetics and pharmacodynamics of warfarin in combina-tion with ambrisentan in healthy volunteers. Br J Clin Pharmacol 2009; 67: 527-34