Current Drug Metabolism

Michael Sinz
Bristol Myers Squibb
Wallingford, CT


Tyrosine Kinase Inhibitors – A Review on Pharmacology, Metabolism and Side Effects

Author(s): Jorg Thomas Hartmann, Michael Haap, Hans-Georg Kopp and Hans-Peter Lipp

Affiliation: Department of Oncology/Hematology/Immunology/Rheumatology/Pneumology, South West German Cancer Center, Eberhard Karls University Tubingen, Otfried- Muller-Strasse 10, 72076 Tubingen, Germany.


Tyrosine kinase inhibitors (TKI) are effective in the targeted treatment of various malignancies. Imatinib was the first to be introduced into clinical oncology, and it was followed by drugs such as gefitinib, erlotinib, sorafenib, sunitinib, and dasatinib. Although they share the same mechanism of action, namely competitive ATP inhibition at the catalytic binding site of tyrosine kinase, they differ from each other in the spectrum of targeted kinases, their pharmacokinetics as well as substance-specific adverse effects. With variations from drug to drug, tyrosine kinase inhibitors cause skin toxicity, including folliculitis, in more than 50% of patients. Among the tyrosine kinase inhibitors that are commercially available as yet, the agents that target EGFR, erlotinib and gefitinib, display the broadest spectrum of adverse effects on skin and hair, including folliculitis, paronychia, facial hair growth, facial erythema, and varying forms of frontal alopecia. In contrast, folliculitis is not common during administration of sorafenib and sunitinib, which target VEGFR, PDGFR, FLT3, and others, whereas both agents have been associated with subungual splinter hemorrhages. Periorbital edema is a common adverse effect of imatinib. Besides the haematological side effects of most of TKIs like anemia, thrombopenia and neutropenia, the most common extraheamatologic adverse effects are edema, nausea, hypothyroidism, vomiting and diarrhea. Regarding possible long term effects, recently cardiac toxicity with congestive heart failure is under debate in patients receiving imatinib and sunitinib therapy; however, this observation was probably relate to patients selection, although, TKIs overall appear to be a very well tolerated drug class.

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Article Details

Page: [470 - 481]
Pages: 12
DOI: 10.2174/138920009788897975