Population pharmacokinetics of dabrafenib, a BRAF inhibitor: Effect of dose, time, covariates, and relationship with its metabolites

Journal of Clinical Pharmacology

Volumn 54, Issue 6, 2014, Pages 696-706

  Ouellet, Daniele ^a   Gibiansky, Ekaterina ^b   Leonowens, Cathrine ^a   O'Hagan, Anne ^a   Haney, Patricia ^a   Switzky, Julie ^a   Goodman, Vicki L ^a  

^a GLAXOSMITHKLINE   (United States)

^b QuantPharm LLC 49 Flints Grove Drive   (United States)

Author keywords

dabrafenib; induction; metabolites; NONMEM; pharmacokinetics

Indexed keywords

DABRAFENIB; GELATIN; HYDROXYPROPYLMETHYLCELLULOSE; ANTINEOPLASTIC AGENT; B RAF KINASE; IMIDAZOLE DERIVATIVE; OXIME; PROTEIN KINASE INHIBITOR;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; BODY WEIGHT; CONCENTRATION RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG HALF LIFE; FEMALE; GENDER; HUMAN; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MELANOMA; PHASE 3 CLINICAL TRIAL; POPULATION RESEARCH; REPEATED DRUG DOSE; SINGLE DRUG DOSE; STEADY STATE; TIME TO MAXIMUM PLASMA CONCENTRATION; VERY ELDERLY; ANTAGONISTS AND INHIBITORS; BIOLOGICAL MODEL; BLOOD; CHEMISTRY; CLINICAL TRIAL; DOSE RESPONSE; DRUG ADMINISTRATION; MIDDLE AGED; MULTICENTER STUDY; YOUNG ADULT;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; GELATIN; HUMANS; HYPROMELLOSE DERIVATIVES; IMIDAZOLES; MALE; MIDDLE AGED; MODELS, BIOLOGICAL; OXIMES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS B-RAF; YOUNG ADULT;

EID: 84899829467     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1002/jcph.263     Document Type: Article

References (24)

1. King AJ, Arnone MR, Bleam MR, et al. Dabrafenib; preclinical characterization, increased efficacy when combined with trametinib, while BRAF/MEK tool combination reduced skin lesions. PLoS ONE. 2013; 8 (7): e67583 DOI: 10.1371/journal.pone.0067583.
2. Falchook GS, Long GV, Kurzrock R, et al. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: A phase 1 dose-escalation trial. Lancet. 2012; 379 (9829): 1893-1901.
3. Ascierto PA, Minor D, Ribas A, et al. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol. DOI: 10.1200/JCO.2013.49.8691.
4. Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012; 380 (9839): 358-365 DOI: 10.1016/S0140-6736(12)60868-X.
5. Long GV, Trefzer U, Davies MA, et al. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2012; 13 (11): 1087-1095.
6. Ouellet D, Grossmann KF, Limentani G, et al. Effects of particle size, food and capsule shell composition on the oral bioavailability of dabrafenib, a BRAF inhibitor, in patients with BRAF mutation-positive tumors. J Pharm Sci. 2013.
7. Tafinlar Prescribing Information (initial US approval 2013). GlaxoSmithKline, Research Triangle Park, May 2013.
8. Bershas DA, Ouellet D, Mamaril-Fishman DB, et al. Metabolism and disposition of oral dabrafenib in cancer patients: proposed participation of aryl nitrogen in carbon-carbon bond cleavage via decarboxylation following enzymatic oxidation. Drug Metabol Dispos. 2013; 41 (12): 2215-2224.
9. Beal S, Sheiner LB, Boeckmann A,. NONMEM User's Guides. Icon Development Solutions Ellicott City, Maryland, USA: 2011.
10. Harrell FE,. Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. New York: Springer-Verlag; 2001.
11. Wahlby U, Jonsson EN, Karlsson MO,. Assessment of actual significance levels for covariate effects in NONMEM. J Pharmacokinet Pharmacodyn. 2001; 28 (3): 231-252.
12. Wahlby U, Bouw MR, Jonsson EN, Karlsson MO,. Assessment of type I error rates for the statistical sub-model in NONMEM. J Pharmacokinet Pharmacodyn. 2002; 29 (3): 251-269.
13. Karlsson MO, Savic RM,. Diagnosing model diagnostics. Clin Pharmacol Ther. 2007; 82: 17-20.
14. Yano Y, Beal SL, Sheiner LB,. Evaluating pharmacokinetic/pharmacodynamic models using the posterior predictive check. J Pharmacokinet Pharmacodyn. 2001; 28: 171-192.
15. Wang DD, Zhang S,. Standardized Visual Predictive Check-How and When to use it in Model Evaluation, PAGE 18. 2009;Abstract 1501 [ www.page-meeting.org/ abstract=1501 ].
16. Bergstrand M, Hooker AC, Allini JE, Karlsson MO,. Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models. AAPS J. 2011; 13 (2): 143-151.
17. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D,. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999; 130 (6): 461-470.
18. National Cancer Institute Protocol Template http://ctep.cancer.gov/ protocoldevelopment/docs/hepatic-dysfunction-v3.doc; accessed Sept 2013.
19. Yang J, Liao M, Shou M, et al. Cytochrome P450 turnover: regulation of synthesis and degradation, metholds for determining rates, and implications for the prediction of drug interactions. Curr Drug Metab. 2008; 9 (5): 384-393.
20. Tran JQ, Kovacs SJ, McIntosh TS, Davis HM, Martin DE,. Morning spot and 24-hour urinary 6 beta-hydroxycortisol to cortisol ratios: intraindividual variability and correlation under basal conditions and conditions of CYP3A isozymes induction. J Clin Pharmacol. 1999; 39: 487-494.
21. Denton CL, Minthorn E, Carson SW, et al. Concomitant oral and intravenous pharmacokinetics of dabrafenib, a BRAF inhibitor, in patients with BRAF V600 mutation-positive solid tumors. J Clin Pharmacol. 2013; 53 (9): 955-961.
22. Nebot N, Chiu JS, Ma B, et al. Exposure-response analysis of the effect of dabrafenib, a braf inhibitor, on tumor size in patients with V600 braf mutation positive melanoma. Clin Pharmacol Ther. 93 (Suppl. 1): S51.
23. Nebot N, Ma B, Haney P, et al. Exposure-response modeling of the effect of dabrafenib, a braf inhibitor, on objective response rate (ORR) in patients with braf V600 mutation positive melanoma. Clin Pharmacol Ther. 93 (Suppl. 1): S65.
24. Shi S, Klotz U,. Age-related changes in pharmacokinetics. Curr Drug Metab. 2011; 12: 601-610.