Sorafenib is a tyrosin kinase inhibitor used to treat renal cell carcinoma and hepatocellular carcinoma. It works by inhibiting multiple intracellular and cell surface kinases involved in tumor signaling, angiogenesis, and apoptosis. Sorafenib is administered orally, with a bioavailability of 38-49% and a half-life of 25-48 hours. It is metabolized in the liver and excreted primarily in feces. Common adverse effects include diarrhea, fatigue, hand-foot syndrome, and hypertension. Sorafenib is contraindicated in patients with known hypersensitivity to the drug.

1. Sufyan Ali
PHMY02213006
M.Phill Pharmacology
Anti-Cancer Drug: Sorafenib
Department Of Pharmacy
The University Of Lahore

2. Sorafenib
Drug class: Tyrosin Kinase Inhibitor
Introduction:
Sorafanib is oral serine/threonine and tyrosin kinase inhibitor used mainly in renal cell
carcinoma. Sorafanib is also part of the treatment strategy for hepatocellular caricinoma.
Sorafanib target the cell surface kinase that are involved in tumor signalling, angiogenesis
and apoptosis, thus slowing tumor growth.
Mechanism of action:
Sorafenib interacts with multiple intracellular (CRAF, BRAF and mutant BRAF) and cell
surface kinases (KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-ß). Several of these kinases
are thought to be involved in angiogenesis, thus sorafenib reduces blood flow to the tumor.
Sorafenib is unique in targeting the Raf/Mek/Erk pathway. By inhibiting these kinases,
genetic transcription involving cell proliferation and angiogenesis is inhibited.
Pharmacokinetics:
The mean relative bioavailability is 38-49% for the tablet form. Sorafenib reached peak
plasma levels in 3 hours following oral administration. With a high-fat meal, bioavailability
is reduced by 29% compared to administration in the fasted state.99.5% bound to plasma
proteins.
Sorafenib is metabolized primarily in the liver, undergoing oxidative metabolism, mediated
by CYP3A4, as well as glucuronidation mediated by UGT1A9.
Following oral administration of a 100 mg dose of a solution formulation of sorafenib, 96%
of the dose was recovered within 14 days, with 77% of the dose excreted in feces, and 19% of
the dose excreted in urine as glucuronidated metabolites. Its half-life is 25-48 hours.

3. Toxicity:
The highest dose of sorafenib studied clinically is 800 mg twice daily. The adverse reactions
observed at this dose were primarily diarrhea and dermatologic events
Indications:
Sorafenib is indicated for the treatment of unresectable hepatocellular carcinoma and
advanced renal cell carcinoma
Adverse drug reactions:
 Diarrhea
 Fatigue
 Hand and foot syndrome
 Hypertension
Contraindictions:
Sorafenib is contraindicated in patients with known hypersensitivity to Sorafenib . In
combination with carboplatin and paclitaxel with squamous cell lung cancer