Population pharmacokinetic analysis of sorafenib in patients with solid tumours

British Journal of Clinical Pharmacology

Volumn 72, Issue 2, 2011, Pages 294-305

  Jain, Lokesh ^a,e   Woo, Sukyung ^a   Gardner, Erin R ^c   Dahut, William L ^b   Kohn, Elise C ^b   Kummar, Shivaani ^b   Mould, Diane R ^d   Giaccone, Giuseppe ^b   Yarchoan, Robert ^b   Venitz, Jürgen ^e   Figg, William D ^a,b,e  

^a Clinical Pharmacology Program   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

^c SAIC FREDERICK INC   (United States)

^d Projections Research Inc   (United States)

^e VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

Author keywords

CYP3A4; Population pharmacokinetics; Sorafenib; Tyrosine kinase inhibitor; UGT1A9

Indexed keywords

BEVACIZUMAB; CETUXIMAB; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; GLUCURONOSYLTRANSFERASE 1A9; PROTEINASE INHIBITOR; SORAFENIB;

ADULT; AGED; ARTICLE; BLOOD SAMPLING; BODY WEIGHT; DEMOGRAPHY; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISPOSITION; ENTEROHEPATIC CIRCULATION; GALLBLADDER EMPTYING; GENOTYPE; HUMAN; KAPOSI SARCOMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; SOLID TUMOR; TIME TO MAXIMUM PLASMA CONCENTRATION;

AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; BENZENESULFONATES; CARCINOMA, HEPATOCELLULAR; CARCINOMA, RENAL CELL; CYTOCHROME P-450 CYP3A; FEMALE; GLUCURONOSYLTRANSFERASE; HUMANS; LIVER NEOPLASMS; MALE; MIDDLE AGED; MODELS, THEORETICAL; PROTEIN-TYROSINE KINASES; PYRIDINES; STATISTICS AS TOPIC;

EID: 79960151990     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2011.03963.x     Document Type: Article

References (35)

1. Onyx Pharmaceuticals. Nexavar (Sorafenib) tablets. Available at (last accessed 8 July 2010).
2. Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, Schwartz B, Simantov R, Kelley S. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov 2006; 5: 835-44.
3. Bayer Pharmaceuticals. Nexavar (Sorafenib) Prescribing Information. Available at (last accessed 8 July 2010).
4. Awada A, Hendlisz A, Gil T, Bartholomeus S, Mano M, de Valeriola D, Strumberg D, Brendel E, Haase CG, Schwartz B, Piccart M. Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer 2005; 92: 1855-61.
5. Clark JW, Eder JP, Ryan D, Lathia C, Lenz HJ. Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors. Clin Cancer Res 2005; 11: 5472-80.
6. Moore M, Hirte HW, Siu L, Oza A, Hotte SJ, Petrenciuc O, Cihon F, Lathia C, Schwartz B. Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol 2005; 16: 1688-94.
7. Strumberg D, Clark JW, Awada A, Moore MJ, Richly H, Hendlisz A, Hirte HW, Eder JP, Lenz HJ, Schwartz B. Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist 2007; 12: 426-37.
8. Strumberg D, Richly H, Hilger RA, Schleucher N, Korfee S, Tewes M, Faghih M, Brendel E, Voliotis D, Haase CG, Schwartz B, Awada A, Voigtmann R, Scheulen ME, Seeber S. Phase I clinical and pharmacokinetic study of the novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol 2005; 23: 965-72.
9. Nexavar: European Public Assessment Reports (EPAR)-Scientific Discussion. European Medicines Agency (EMA). Available at (last accessed 1 April 2011).
10. Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995; 12: 413-20.
11. He P, Court MH, Greenblatt DJ, Von Moltke LL. Genotype-phenotype associations of cytochrome P450 3A4 and 3A5 polymorphism with midazolam clearance in vivo. Clin Pharmacol Ther 2005; 77: 373-87.
12. Bosch TM, Meijerman I, Beijnen JH, Schellens JH. Genetic polymorphisms of drug-metabolising enzymes and drug transporters in the chemotherapeutic treatment of cancer. Clin Pharmacokinet 2006; 45: 253-85.
13. Domanski TL, Finta C, Halpert JR, Zaphiropoulos PG. cDNA cloning and initial characterization of CYP3A43, a novel human cytochrome P450. Mol Pharmacol 2001; 59: 386-92.
14. Gomo C, Coriat R, Faivre L, Mir O, Ropert S, Billemont B, Dauphin A, Tod M, Goldwasser F, Blanchet B. Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs 2010. DOI: 10.1007/s10637-010-9514-3.
15. Girard H, Court MH, Bernard O, Fortier LC, Villeneuve L, Hao Q, Greenblatt DJ, von Moltke LL, Perussed L, Guillemette C. Identification of common polymorphisms in the promoter of the UGT1A9 gene: evidence that UGT1A9 protein and activity levels are strongly genetically controlled in the liver. Pharmacogenetics 2004; 14: 501-15.
16. Mross K, Steinbild S, Baas F, Gmehling D, Radtke M, Voliotis D, Brendel E, Christensen O, Unger C. Results from an in vitro and a clinical/pharmacological phase I study with the combination irinotecan and sorafenib. Eur J Cancer 2007; 13: 55-63.
17. Villeneuve L, Girard H, Fortier LC, Gagne JF, Guillemette C. Novel functional polymorphisms in the UGT1A7 and UGT1A9 glucuronidating enzymes in Caucasian and African-American subjects and their impact on the metabolism of 7-ethyl-10-hydroxycamptothecin and flavopiridol anticancer drugs. J Pharmacol Exp Ther 2003; 307: 117-28.
18. Paoluzzi L, Singh AS, Price DK, Danesi R, Mathijssen RH, Verweij J, Figg WD, Sparreboom A. Influence of genetic variants in UGT1A1 and UGT1A9 on the in vivo glucuronidation of SN-38. J Clin Pharmacol 2004; 44: 854-60.
19. Lepper ER, Baker SD, Permenter M, Ries N, van Schaik RH, Schenk PW, Price DK, Ahn D, Smith NF, Cusatis G, Ingersoll RG, Bates SE, Mathijssen RH, Verweij J, Figg WD, Sparreboom A. Effect of common CYP3A4 and CYP3A5 variants on the pharmacokinetics of the cytochrome P450 3A phenotyping probe midazolam in cancer patients. Clin Cancer Res 2005; 11: 7398-404.
20. Jain L, Gardner ER, Venitz J, Dahut W, Figg WD. Development of a rapid and sensitive LC-MS/MS assay for the determination of sorafenib in human plasma. J Pharm Biomed Anal 2008; 46: 362-7.
21. Bonate PL, Floret S, Bentzen C. Population pharmacokinetics of APOMINE: a meta-analysis in cancer patients and healthy males. Br J Clin Pharmacol 2004; 58: 142-55.
22. NMusers (NONMEM UsersNet Archive). Adaptation of multiple-dose enterohepatic circulation model suggested by Luann Phillips (after Stuart Beal). (11 June 2002).
23. Jiao Z, Ding JJ, Shen J, Liang HQ, Zhong LJ, Wang Y, Zhong MK, Lu WY. Population pharmacokinetic modelling for enterohepatic circulation of mycophenolic acid in healthy Chinese and the influence of polymorphisms in UGT1A9. Br J Clin Pharmacol 2008; 65: 893-907.
24. Moon YJ, Wang L, DiCenzo R, Morris ME. Quercetin pharmacokinetics in humans. Biopharm Drug Dispos 2008; 29: 205-17.
25. Mould DR, Sweeney K, Duffull SB, Neylon E, Hamlin P, Horwitz S, Sirotnak F, Fleisher M, Saunders ME, O'Connor OA. A population pharmacokinetic and pharmacodynamic evaluation of pralatrexate in patients with relapsed or refractory non-Hodgkin's or Hodgkin's lymphoma. Clin Pharmacol Ther 2009; 86: 190-6.
26. Savic RM, Karlsson MO. Importance of shrinkage in empirical bayes estimates for diagnostics: problems and solutions. AAPS J 2009; 11: 558-69.
27. West GB, Brown JH, Enquist BJ. A general model for the origin of allometric scaling laws in biology. Science 1997; 276: 122-6.
28. Drug Bank. Sorafenib drug card DB00398. Available at (last accessed 8 July 2010).
29. Rajagopalan P, Lathia C, Sundaresan P. Population Pharmacokinetics of Sorafenib in Cancer Patients. San Diego, CA: American Association of Pharmaceutical Sciences (AAPS), 2007.
30. Lathia C, Lettieri J, Cihon F, Gallentine M, Radtke M, Sundaresan P. Lack of effect of ketoconazole-mediated CYP3A inhibition on sorafenib clinical pharmacokinetics. Cancer Chemother Pharmacol 2006; 57: 685-92.
31. Miller AA, Murry DJ, Owzar K, Hollis DR, Kennedy EB, Abou-Alfa G, Desai A, Hwang J, Villalona-Calero MA, Dees EC, Lewis LD, Fakih MG, Edelman MJ, Millard F, Frank RC, Hohl RJ, Ratain MJ. Phase I and pharmacokinetic study of sorafenib in patients with hepatic or renal dysfunction: CALGB 60301. J Clin Oncol 2009; 27: 1800-5.
32. Bonate PL. Pharmacokinetic-Pharmacodynamic Modeling and Simulation, 1st edn. New York: Springer, 2006; 248-9.
33. Savic RM, Jonker DM, Kerbusch T, Karlsson MO. Implementation of a transit compartment model for describing drug absorption in pharmacokinetic studies. J Pharmacokinet Pharmacodyn 2007; 34: 711-26.
34. Ette EI, Williams PJ, eds. Pharmacometrics: The Science of Quantitative Pharmacology. New Jersey: Wiley, John & Sons, Incorporated, 2007; 351-59.
35. Karlsson MO, Beal SL, Sheiner LB. Three new residual error models for population PK/PD analyses. J Pharmacokinet Biopharm 1995; 23: 651-72.