Concomitant oral and intravenous pharmacokinetics of dabrafenib, a BRAF inhibitor, in patients with BRAF V600 mutation-positive solid tumors

Journal of Clinical Pharmacology

Volumn 53, Issue 9, 2013, Pages 955-961

  Denton, Cathrine L ^a   Minthorn, Elisabeth ^a   Carson, Stanley W ^a   Young, Graeme C ^b   Richards peterson, Lauren E ^a   Botbyl, Jeffrey ^c   Han, Chao ^d   Morrison, Royce A ^e   Blackman, Samuel C ^f   Ouellet, Daniele ^a  

^a GLAXOSMITHKLINE   (United States)

^b GLAXOSMITHKLINE   (United Kingdom)

^c Comprehensive Clinical Development ^*

^d Janssen R and D US   (United States)

^e NONE   (United States)

^f SEATTLE GENETICS INC   (United States)

Author keywords

Bioavailability; Dabrafenib; Intravenous; Microtracer; Pharmacokinetic

Indexed keywords

B RAF KINASE; CARBON 14; DABRAFENIB;

ADULT; ANIMAL EXPERIMENT; ARTICLE; CASE REPORT; DISTRIBUTION VOLUME; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG HALF LIFE; FEMALE; FIRST PASS EFFECT; FLUSHING; GENE MUTATION; HUMAN; ISOTOPE LABELING; LUNG SMALL CELL CANCER; MALE; MAXIMUM PLASMA CONCENTRATION; MEAN RESIDENCE TIME; MELANOMA; MOUSE; NONHUMAN; PHASE 1 CLINICAL TRIAL; RADIOACTIVITY; RAT; SIDE EFFECT; TIME TO MAXIMUM PLASMA CONCENTRATION; UPPER RESPIRATORY TRACT INFECTION;

BIOAVAILABILITY; DABRAFENIB; INTRAVENOUS; MICROTRACER; PHARMACOKINETIC;

ADMINISTRATION, INTRAVENOUS; ADMINISTRATION, ORAL; BIOLOGICAL AVAILABILITY; FEMALE; HUMANS; IMIDAZOLES; MALE; MUTATION; NEOPLASMS; OXIMES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS B-RAF;

EID: 84885050585     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1002/jcph.127     Document Type: Article

References (14)

1. 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.
2. Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAFmutated metastatic melanoma: A multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358-365.
3. Trefzer U, Minor D, Ribas A, et al. BREAK-2: A phase IIA trial of the selective BRAF kinase inhibitor GSK2118436 in patients with BRAF mutation-positive (V600E/K) metastatic melanoma. Pigment Cell Melanoma Res. 2011;24(5): Abstr LBA1-1.
4. Nebot N, Richards-Peterson LE, Bershas DA, et al. Characterization of the absorption, distribution, metabolism and elimination of a single oral 14C labeled dose of dabrafenib in subjects with BRAF V600-mutation positive solid tumors. Clin Pharmacol Ther. 2013;93(S52-S86): PII-38.
5. Department of Health and Human Services, Center for Drug Evaluation and Research (CDER). FDA guidance for industry: bioavailability and bioequivalence studies for orally administered drug products - general considerations. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/ucm070124.pdf. Updated 2003. Accessed February 26, 2013.
6. European Medicines Agency (EMEA). Committee for Medicinal Products for Human Use (CHMP). Position paper on non-clinical safety studies to support clinical trials with a single microdose. http://www.ema.europa.eu/ema/index.jsp? curl1/4pages/regulation/general/general-content-000400.jsp&mid1/ 4WC0b01ac0580029570. Updated 2004. Accessed February 26, 2013.
7. Boulton DW, Kasichayanula S, Keung CF, et al. Simultaneous oral therapeutic and intravenous (14) C-microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin. Br J Clin Pharmacol. 2013;75(3):763-768.
8. Hoffmann E, Wald J, Lavu S, et al. Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule activator of SIRT1, after single and repeated oral administration in man. Br J Clin Pharmacol. 2013;75(1):186-196.
9. Lappin G, Shishikura Y, Jochemsen R, et al. Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability. Eur J Pharm Sci. 2010;40(2):125-131.
10. Sarapa N, Hsyu PH, Lappin G, Garner RC. The application of accelerator mass spectrometry to absolute bioavailability studies in humans: simultaneous administration of an intravenous microdose of 14C-nelfinavir mesylate solution and oral nelfinavir to healthy volunteers. J Clin Pharmacol. 2005;45(10):1198-1205. (Pubitemid 41361920)
11. Zhou XJ, Garner RC, Nicholson S, Kissling CJ, Mayers D. Microdose pharmacokinetics of IDX899 and IDX989, candidate HIV-1 non-nucleoside reverse transcriptase inhibitors, following oral and intravenous administration in healthy male subjects. J Clin Pharmacol. 2009;49(12):1408-1416.
12. Young GC, Corless S, Felgate CC, Colthup PV. Comparison of a 250 kV single-stage accelerator mass spectrometer with a 5 MV tandem accelerator mass spectrometer-fitness for purpose in bioanalysis. Rapid Commun Mass Spectrom. 2008;22(24):4035-4042.
13. Denton CL, Carson SW, Young GC, et al. Absolute bioavailability of BRAF inhibitor GS K2118436: use of a microtracer study in patients with cancer. Cancer Res. 2012;72: Abstr 3773.
14. Rowland M, Tozer TN. Clinical pharmacokinetics: concepts and applications. 2nd ed. Philadelphia, PA: Lea & Febiger; 1989.