Population pharmacokinetic analysis of axitinib in healthy volunteers

British Journal of Clinical Pharmacology

Volumn 77, Issue 3, 2014, Pages 480-492

  Garrett, May ^a   Poland, Bill ^b   Brennan, Meghan ^a   Hee, Brian ^a   Pithavala, Yazdi K ^a   Amantea, Michael A ^a  

^a PFIZER INC   (United States)

^b Pharsight   (United States)

Author keywords

28 genotype; axitinib; CYP2C19 metabolizing status; population pharmacokinetics; UGT1A1; vascular endothelial growth factor receptor inhibitor

Indexed keywords

AXITINIB; CYP2C19 METABOLIZING STATUS; POPULATION PHARMACOKINETICS; UGT1A1*28 GENOTYPE; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR INHIBITOR;

ADULT; ANGIOGENESIS INHIBITORS; ARYL HYDROCARBON HYDROXYLASES; BIOTRANSFORMATION; BODY WEIGHT; CLINICAL TRIALS, PHASE I AS TOPIC; DRUG DOSAGE CALCULATIONS; FEMALE; GENOTYPE; GLUCURONOSYLTRANSFERASE; HEALTHY VOLUNTEERS; HUMANS; IMIDAZOLES; INDAZOLES; MALE; MIDDLE AGED; MODELS, BIOLOGICAL; NONLINEAR DYNAMICS; PHARMACOGENETICS; PHENOTYPE; PROTEIN KINASE INHIBITORS; YOUNG ADULT;

EID: 84894490360     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/bcp.12206     Document Type: Article

References (46)

1. Hu-Lowe DD, Zou HY, Grazzini ML, Hallin ME, Wickman GR, Amundson K, Chen JH, Rewolinski DA, Yamazaki S, Wu EY, McTigue MA, Murray BW, Kania RS, O'Connor P, Shalinsky DR, Bender SL,. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res 2008; 14: 7272-7283.
2. Choueiri TK,. Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. Curr Opin Investig Drugs 2008; 9: 658-671.
3. Kelly RJ, Rixe O,. Axitinib-a selective inhibitor of the vascular endothelial growth factor (VEGF) receptor. Target Oncol 2009; 4: 297-305.
4. Rixe O, Bukowski RM, Michaelson MD, Wilding G, Hudes GR, Bolte O, Motzer RJ, Bycott P, Liau KF, Freddo J, Trask PC, Kim S, Rini BI,. Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol 2007; 8: 975-984.
5. Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, Kane MA, Sherman E, Kim S, Bycott P, Tortorici M, Shalinsky DR, Liau KF, Cohen RB,. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol 2008; 26: 4708-4713.
6. Rini BI, Wilding G, Hudes G, Stadler WM, Kim S, Tarazi J, Rosbrook B, Trask PC, Wood L, Dutcher JP,. Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. J Clin Oncol 2009; 27: 4462-4468.
7. Schiller JH, Larson T, Ou SH, Limentani S, Sandler A, Vokes E, Kim S, Liau K, Bycott P, Olszanski AJ, von Pawel J,. Efficacy and safety of axitinib in patients with advanced non-small-cell lung cancer: results from a phase II study. J Clin Oncol 2009; 27: 3836-3841.
8. Bhojani N, Jeldres C, Patard JJ, Perrotte P, Suardi N, Hutterer G, Patenaude F, Oudard S, Karakiewicz PI,. Toxicities associated with the administration of sorafenib, sunitinib, and temsirolimus and their management in patients with metastatic renal cell carcinoma. Eur Urol 2008; 53: 917-930.
9. Hutson TE, Figlin RA, Kuhn JG, Motzer RJ,. Targeted therapies for metastatic renal cell carcinoma: an overview of toxicity and dosing strategies. Oncologist 2008; 13: 1084-1096.
10. Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou Y-C, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ,. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011; 378: 1931-1939.
11. Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, Pithavala YK, Reich SD, Freddo JL, Wilding G,. Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol 2005; 23: 5474-5483.
12. Zientek M, Kang P, Jiang Y, Smith B,. In vitro kinetic characterization of axitinib metabolism to estimate the clinical implications of genetic polymorphisms. Proceedings of the International Meeting of the International Society for the Study of Xenobiotics: Genetic Polymorphisms in Drug Disposition Workshop; 2010 April 11-13; Indianapolis, IN.
13. Center for Drug Evaluation and Research. Clinical pharmacology review: Inlyta. In: Summary Basis for Approval, Clinical Pharmacology and Biopharmaceutics Review. Document # 202324Orig1s000. US Department Health and Human Services Food and Drug Administration, 2011. Available at http://www.accessdata.fda.gov/drugsatfda-docs/nda/2012/ 202324Orig1s000ClinPharmR.pdf (last accessed 9 October 2012).
14. Pithavala YK, Tong W, Mount J, Rahavendran SV, Garrett M, Hee B, Selaru P, Sarapa N, Klamerus KJ,. Effect of ketoconazole on the pharmacokinetics of axitinib in healthy volunteers. Invest New Drugs 2012; 30: 273-281.
15. Pithavala YK, Chen Y, Toh M, Selaru P, Labadie R, Garrett M, Hee B, Mount J, Ni G, Klamerus KJ, Tortorici MA,. Evaluation of the effect of food on the pharmacokinetics of axitinib in healthy volunteers. Cancer Chemother Pharmacol 2012; 70: 103-112.
16. Pithavala YK, Tortorici M, Toh M, Garrett M, Hee B, Kuruganti U, Ni G, Klamerus KJ,. Effect of rifampin on the pharmacokinetics of axitinib (AG-013736) in Japanese and Caucasian healthy volunteers. Cancer Chemother Pharmacol 2010; 65: 563-570.
17. Chen Y, Jiang J, Zhang J, Tortorici MA, Pithavala YK, Lu L, Ni G, Hu P,. A Phase I study to evaluate the pharmacokinetics of axitinib (AG-13736) in healthy Chinese volunteers. Int J Clin Pharmacol Ther 2011; 49: 679-687.
18. Tortorici MA, Toh M, Rahavendran SV, Labadie RR, Alvey CW, Marbury T, Fuentes E, Green M, Ni G, Hee B, Pithavala YK,. Influence of mild and moderate hepatic impairment on axitinib pharmacokinetics. Invest New Drugs 2011; 29: 1370-1380.
19. Martin LP, Kozloff MF, Herbst RS, Samuel TA, Kim S, Rosbrook B, Tortorici M, Chen Y, Tarazi J, Olszanski AJ, Rado T, Starr A, Cohen RB,. Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours. Br J Cancer 2012; 107: 1268-1276.
20. Mukohara T, Nakajima H, Mukai H, Nagai S, Itoh K, Umeyama Y, Hashimoto J, Minami H,. Effect of axitinib (AG-013736) on fatigue, thyroid-stimulating hormone, and biomarkers: a phase I study in Japanese patients. Cancer Sci 2010; 101: 963-968.
21. Fujiwara Y, Kiyota N, Chayahara N, Suzuki A, Umeyama Y, Mukohara T, Minami H,. Management of axitinib (AG-013736)-induced fatigue and thyroid dysfunction, and predictive biomarkers of axitinib exposure: results from phase I studies in Japanese patients. Invest New Drugs 2012; 30: 1055-1064.
22. Kozloff MF, Martin LP, Krzakowski M, Samuel TA, Rado TA, Arriola E, De Castro Carpeno J, Herbst RS, Tarazi J, Kim S, Rosbrook B, Tortorici M, Olszanski AJ, Cohen RB,. Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours. Br J Cancer 2012; 107: 1277-1285.
23. Demetri GD, Wang Y, Wehrle E, Racine A, Nikolova Z, Blanke CD, Joensuu H, von Mehren M,. Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors. J Clin Oncol 2009; 27: 3141-3147.
24. Houk BE, Bello CL, Kang D, Amantea M,. A population pharmacokinetic meta-analysis of sunitinib malate (SU11248) and its primary metabolite (SU12662) in healthy volunteers and oncology patients. Clin Cancer Res 2009; 15: 2497-2506.
25. Jain L, Woo S, Gardner ER, Dahut WL, Kohn EC, Kummar S, Mould DR, Giaccone G, Yarchoan R, Venitz J, Figg WD,. Population pharmacokinetic analysis of sorafenib in patients with solid tumors. Br J Clin Pharmacol 2011; 72: 294-305.
26. Lyamichev V, Brow MA, Dahlberg JE,. Structure-specific endonucleolytic cleavage of nucleic acids by eubacterial DNA polymerases. Science 1993; 260: 778-783.
27. Rousseau A, Leger F, Le Meur Y, Saint-Marcoux F, Paintaud G, Buchler M, Marquet P,. Population pharmacokinetic modeling of oral cyclosporin using NONMEM: comparison of absorption pharmacokinetic models and design of a Bayesian estimator. Ther Drug Monit 2004; 26: 23-30.
28. Duval V, Karlsson MO,. Impact of omission or replacement of data below the limit of quantification on parameter estimates in a two-compartment model. Pharm Res 2002; 19: 1835-1840.
29. Garrett M, Amantea MA, Pithavala YK, Ruiz A,. Evaluation of the impact of omitting drug concentraion data below the lower limit of quantification (LLOQ) on the pharmacokinetics of axitinib (AG-013736), an anti-angiogenic agent. Clin Pharmacol Ther 2010; 87: (Suppl. 1; abstr PIII-33): S78-79.
30. Savic RM, Karlsson MO,. Importance of shrinkage in empirical Bayes estimates for diagnostics: problems and solutions. AAPS J 2009; 11: 558-569.
31. Rini BI, Garrett M, Poland B, Dutcher JP, Rixe O, Wilding G, Stadler WM, Pithavala YK, Kim S, Tarazi J, Motzer RJ,. Axitinib in metastatic renal cell carcinoma: results of a pharmacokinetic and pharmacodynamic analysis. J Clin Pharmacol 2013; 53: 491-504.
32. van Erp N, Gelderblom H, van Glabbeke M, Van Oosterom A, Verweij J, Guchelaar HJ, Debiec-Rychter M, Peng B, Blay JY, Judson I,. Effect of cigarette smoking on imatinib in patients in the soft tissue and bone sarcoma group of the EORTC. Clin Cancer Res 2008; 14: 8308-8313.
33. Lamba JK, Lin YS, Schuetz EG, Thummel KE,. Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 2002; 54: 1271-1294.
34. Dai D, Tang J, Rose R, Hodgson E, Bienstock RJ, Mohrenweiser HW, Goldstein JA,. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J Pharmacol Exp Ther 2001; 299: 825-831.
35. Wojnowski L, Kamdem LK,. Clinical implications of CYP3A polymorphisms. Expert Opin Drug Metab Toxicol 2006; 2: 171-182.
36. Zhao W, Elie V, Roussey G, Brochard K, Niaudet P, Leroy V, Loirat C, Cochat P, Cloarec S, Andre JL, Garaix F, Bensman A, Fakhoury M, Jacqz-Aigrain E,. Population pharmacokinetics and pharmacogenetics of tacrolimus in de novo pediatric kidney transplant recipients. Clin Pharmacol Ther 2009; 86: 609-618.
37. Ando Y, Hasegawa Y,. Clinical pharmacogenetics of irinotecan (CPT-11). Drug Metab Rev 2005; 37: 565-574.
38. Han JY, Lim HS, Shin ES, Yoo YK, Park YH, Lee JE, Jang IJ, Lee DH, Lee JS,. Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small cell lung cancer treated with irinotecan and cisplatin. J Clin Oncol 2006; 24: 2237-2244.
39. Maeda A, Ando H, Asai T, Ishiguro H, Umemoto N, Ohta M, Morishima M, Sumida A, Kobayashi T, Hosohata K, Ushijima K, Fujimura A,. Differential impacts of CYP2C19 gene polymorphisms on the antiplatelet effects of clopidogrel and ticlopidine. Clin Pharmacol Ther 2011; 89: 229-233.
40. Hunfeld NG, Mathot RA, Touw DJ, van Schaik RH, Mulder PG, Franck PF, Kuipers EJ, Geus WP,. Effect of CYP2C19*2 and*17 mutations on pharmacodynamics and kinetics of proton pump inhibitors in Caucasians. Br J Clin Pharmacol 2008; 65: 752-760.
41. Kaniwa N, Kurose K, Jinno H, Tanaka-Kagawa T, Saito Y, Saeki M, Sawada J, Tohkin M, Hasegawa R,. Racial variability in haplotype frequencies of UGT1A1 and glucuronidation activity of a novel single nucleotide polymorphism 686C> T (P229L) found in an African-American. Drug Metab Dispos 2005; 33: 458-465.
42. Liu JY, Qu K, Sferruzza AD, Bender RA,. Distribution of the UGT1A1*28 polymorphism in Caucasian and Asian populations in the US: a genomic analysis of 138 healthy individuals. Anticancer Drugs 2007; 18: 693-696.
43. Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, Lindhout D, Tytgat GN, Jansen PL, Oude Elferink RP, Chowdhury NR,. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med 1995; 333: 1171-1175.
44. Brennan M, Williams JA, Chen Y, Tortorici M, Pithavala Y, Liu YC,. Meta-analysis of contribution of genetic polymorphisms in drug-metabolizing enzymes or transporters to axitinib pharmacokinetics. Eur J Clin Pharmacol 2012; 68: 645-655.
45. Center for Drug Evaluation and Research. Clinical pharmacology review: Sutent. In: Summary Basis for Approval, Clinical Pharmacology and Biopharmaceutics Review. Document # NDA 21-938 (GIST), NDA 21-968 (MRCC). US Department of Health and Human Services Food and Drug Administration, 2005. Available at http://www.accessdata.fda.gov/drugsatfda-docs/nda/2006/021938-S000- Sutent-BioPharmR.pdf (last accessed 9 October 2012).
46. Center for Drug Evaluation and Research. Clinical pharmacology review: Votrient. In: Summary Basis for Approval, Clinical Pharmacology and Biopharmaceutics Review. Document # 22-465. US Department of Health and Human Services Food and Drug Administration, 2008. Avaialble at http://www.accessdata. fda.gov/drugsatfda-docs/nda/2009/022465s000-ClinPharmR.pdf (last accessed 9 October 2012)