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Better Known as: Gleevec
- Marketed By: Novartis
- Major Indication: Leukemia and Gastrointestinal Stromal Tumors
- Drug Class: Receptor Tyrosine Kinase (Especially PDGFR, Abl & KIT) Inhibitor
- Date of FDA Approval (Expiration): 2001 (2015)
- 2009 Global Sales: $3.9 Billion
- Importance: It is one of the best selling cancer drugs of all time. It was the drug to be approved from the tyrosine kinase inhibitor class of drugs. It is very specific receptor tyrosine kinase (RTK) inhibitor, binding to Abl, PDGFR and KIT with far greater specificity than other RTKs, helping explain its relatively low impact side effect profile. Although now considered hyperbole, TIME magazine declared that Gleevec was "converting a fatal cancer into a manageable chronic condition." Has generated significant controversy due to its nearly $65,000 per year cost at a time when global health care budgets are being stretched thin.[1]
- See Pharmaceutical Drugs for more information about other drugs and disorders
Mechanism of Action
[2]
Pharmacokinetics
| Tyrosine Kinase Inhibitor Pharmacokinetics
|
|
| VEGFR & KIT Inhibitors
| EGFR Inhibitors
| BCR-Abl Inhibitor
|
| Parameter
| Sunitinib
(Sutent)
| Sorafenib
(Nexavar)
| Erlotinib
(Tarceva)
| Gefitinib
(Iressa)
| Lapatinib
(Tykerb)
| Imatinib
(Gleevec)
| Nilotinib
(Tasigna)
| Dasatinib
(Sprycel)
|
| Tmax (hr)
| 8
| 8.3
| 2.0
| 5.4
| 4
| 3.7
| 3.0
| 1.0
|
| Cmax (ng/ml)
| 24.6
| 460
| 69.6
| 130
| 115
| 2070
| 411
| 124
|
| Bioavailability (%)
| Variable
| 29-49
| 99
| 59
| Variable
| 98
| 30
| 20
|
| Protein Binding (%)
| 95
| 99
| 93
| 90
| 99
| 95
| 98
| 96
|
| T1/2 (hr)
| 83
| 29
| 9.4
| 26.9
| 9.6
| 26.6
| 16.0
| 3.3
|
| AUC (ng/ml/hr)
| 1921
| 11040
| 20577
| 3850
| 1429
| 4760
| 10052
| 461
|
| Dosage (mg)
| 50
| 50
| 150
| 250
| 100
| 400
| 200
| 200
|
| Metabolism
| Hepatic (CYP3A4)
| Hepatic (CYP3A4)
| Hepatic (CYP3A4)
| Hepatic (CYP3A4)
| Hepatic (CYP3A4)
| Hepatic (CYP3A4)
| Hepatic (CYP3A4)
| Hepatic (CYP3A4)
|
For Pharmacokinetic Data References, see: References
|
References
- ↑ A Conversation With Brian J. Druker, M.D., Researcher Behind the Drug Gleevec by Claudia Dreifus, The New York Times, November 2, 2009
- ↑ Cowan-Jacob SW, Fendrich G, Floersheimer A, Furet P, Liebetanz J, Rummel G, Rheinberger P, Centeleghe M, Fabbro D, Manley PW. Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia. Acta Crystallogr D Biol Crystallogr. 2007 Jan;63(Pt 1):80-93. Epub 2006, Dec 13. PMID:17164530 doi:http://dx.doi.org/10.1107/S0907444906047287
