A randomized, open-label, 5-period, balanced crossover study to evaluate the relative bioavailability of eltrombopag powder for oral suspension (PfOS) and tablet formulations and the effect of a high-calcium meal on eltrombopag pharmacokinetics when administered with or 2 hours before or after PfOS

Clinical Therapeutics

Volumn 34, Issue 3, 2012, Pages 699-709

  Wire, Mary Beth ^a   Bruce, Jennifer ^b   Gauvin, Jennifer ^a   Pendry, Carolyn J ^a   McGuire, Sandra ^a   Qian, Yanwen ^a   Brainsky, Andres ^a  

^a GLAXOSMITHKLINE   (United States)

^b Research Triangle Park   (United States)

Author keywords

Bioavailability; Chelation; Eltrombopag; Food; Pharmacokinetics; Powder for oral suspension

Indexed keywords

CALCIUM; ELTROMBOPAG;

ADULT; AREA UNDER THE CURVE; ARTICLE; CALCIUM INTAKE; COMPARATIVE STUDY; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIAPHORESIS; DIZZINESS; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSAGE FORM COMPARISON; DRUG FORMULATION; DRUG INDUCED HEADACHE; DRUG TOLERABILITY; FEMALE; FOOD DRUG INTERACTION; HEAT SENSATION; HUMAN; HUMAN EXPERIMENT; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; OPEN STUDY; PALLOR; POWDER FOR ORAL SUSPENSION; PRESYNCOPE; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SINGLE DRUG DOSE; TABLET; TIME TO MAXIMUM PLASMA CONCENTRATION; VOMITING;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; BENZOIC ACIDS; BIOLOGICAL AVAILABILITY; CALCIUM; CROSS-OVER STUDIES; FEMALE; FOOD; FOOD-DRUG INTERACTIONS; HUMANS; HYDRAZINES; MALE; MIDDLE AGED; POWDERS; PYRAZOLES; RECEPTORS, THROMBOPOIETIN; SUSPENSIONS; TABLETS; TIME FACTORS; YOUNG ADULT;

EID: 84858592582     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2012.01.011     Document Type: Article

References (28)

1. Jenkins J.M., Williams D., Deng Y., et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood 2007, 109:4739-4741.
2. Cheng G., Saleh M.N., Marcher C., et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet 2011, 377:393-402.
3. Lilleyman J.S. Management of childhood idiopathic thrombocytopenia purpura. Br. J. Haematol 1999, 105:871-875.
4. Williams D.D., Peng B., Bailey C.K., et al. Effects of food and antacids on the pharmacokinetics of eltrombopag in healthy adult subjects: Two single-dose, open-label, randomized-sequence, crossover studies. Clin Ther 2009, 31:764-776.
5. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. Adopted by the 18th World Medical Assemby, Helsinki 1964 as amended by the 48th World Medical Assembly, Somerset West, Republic of South Africa World Medical Association (WMA), Accessed September 20, 2010. http://www.wma.net/en/30publications/10policies/b3/index.html.
6. Ritschel W.A., Kearns G.L. Handbook of Basic Pharmacokinetics 2004, APhA Publications, Washington, DC. 6th ed.
7. Schuirmann D.J. Design of bioavailability/bioequivalence studies. Drug Inf J 1990, 24:315-323.
8. Han L. Calculating the point estimate and confidence interval of Hodges-Lehmann's median using SAS software SUSAG 2008: Proceedings of the SouthEast SAS Users Group, St. Pete Beach, FL, Accessed September 20, 2010. http://analytics.ncsu.edu/sesug/2008/ST-154.pdf.
9. Guidance for industry: Drug-induced liver injury: premarketing clinical evaluation US Department of Health and Human Services, Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), Accessed September 20, 2010. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM174090.pdf.
10. Schmidt L.E., Dalhoff K. Food-drug interactions. Drugs 2002, 62:1481-1502.
11. Wallace A.W., Amsden G.W. Is it really OK to take this with food?. Old interactions with a new twist. J. Clin. Pharmacol 2002, 42:437-443.
12. Guidance for industry: Food-effect bioavailability and fed bioequivalence studies US Department of Health and Human Services, Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), Accessed September 20, 2010. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070241.pdf.
13. Lober S., Ziege S., Rau M., et al. Pharmacokinetics of gatifloxacin and interaction wtih an antacid containing aluminum and magnesium. Antimicrob Agents Chemother 1999, 43:1067-1071.
14. Krishna G., Kisicki J.C., Olsen S., et al. Effect of an aluminum- and magnesium-containing antacid on the bioavailability of garenoxacin in healthy volunteers. Pharmacotherapy 2007, 27:963-969.
15. Nix D.E., Watson W.A., Lener M.E., et al. Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin. Clin Pharmacol Ther 1989, 46:700-705.
16. Allen A., Vousden M., Porter A., Lewis A. Effect of Maalox on the bioavailability of oral gemifloxacin in healthy volunteers. Chemotherapy 1999, 45:504-511.
17. Stass H., Böttcher M.-F., Ochmann K. Evaluation of the influence of antacids and H2 antagonists on the absorption of moxifloxacin after oral administration of a 400 mg dose to healthy volunteers. Clin Pharmacokinet 2001, 40(Suppl 1):39-48.
18. Teng R., Dogolo L.C., Willavize S.A., et al. Effect of Maalox and omeprazole on the bioavailability of trovafloxacin. J Antimicrob Chemother 1997, 39(Suppl B):93-97.
19. Grasela T.H., Schentag J.J., Sedman A.J., et al. Inhibition of enoxacin absorption by antacids or ranitidine. Antimicrob Agents Chemother 1989, 33:615-617.
20. Nix D.E., Wilton J.H., Distlerath L., et al. Inhibition of norfloxacin absorption by antacids. Antimicrob Agents Chemother 1990, 34:432-435.
21. Johnson R.D., Dorr M.B., Talbot G.H., Caille G. Effect of Maalox on the oral absorption of sparfloxacin. Clin Ther 1998, 20:1149-1158.
22. Lazzaroni M., Imbimbo B.P., Bargiggia S., et al. Effects of magnesium-aluminum hydroxide antacid on absorption of rufloxacin. Antimicrob Agents Chemother 1993, 37:2212-2216.
23. Shimada J., Shiba K., Oguma T., et al. Effect of antacid on the absorption of the quinolone lomefloxacin. Antimicrob Agents Chemother 1992, 36:1219-1224.
24. Shiba K., Sakai O., Shimada J., et al. Effects of antacids, ferrous sulfate, and ranitidine on absorption of DR-3355 in humans. Antimicrob Agents Chemother 1992, 36:2270-2274.
25. Flor S., Guay D.R., Opsahl J.A., et al. Effects of magnesium-aluminum hydroxide and calcium carbonate antacids on bioavailability of ofloxacin. Antimicrob Agents Chemother 1990, 34:2436-2438.
26. Granneman G.R., Stephan U., Birner B., et al. Effect of antacid medication on the pharmacokinetics of temafloxacin. Clin Pharmacokinet 1992, 22(Suppl 1):83-89.
27. McHutchison J.G., Dusheiko G., Shiffman M.L., et al. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med 2007, 357:2227-2236.
28. Matthys G., Park J.W., McGuire S., et al. Clinical pharmacokinetics, platelet response, and safety of eltrombopag at supratherapeutic doses of up to 200 mg once daily in healthy volunteers. J Clin Pharmacol 2011, 51:301-308.