Pharmacokinetics
After tivozanib is taken by mouth, highest blood serum levels are reached after 2 to 24 hours. The total AUC is independent of food intake. When in the bloodstream, over 99% of the substance are bound to plasma proteins, predominantly albumin. Although the enzymes CYP3A4 and CYP1A1 and several UGTs are capable of metabolising the drug, over 90% circulate in unchanged form. The metabolites are demethylation, hydroxylation and N-oxidation products and glucuronides.The biological half-life is 4.5 to 5.1 days; 79% being excreted via the faeces, mostly unchanged, and 12% via the urine, completely unchanged. Chemistry
Tivozanib is used in form of the hydrochloride monohydrate, which is a white to light brown powder. It is practically insoluble in water and has low solubility in aqueous acids, ethanol and methanol. It is not hygroscopic and not optically active. History
It was discovered by Kyowa Kirin and developed by AVEO Pharmaceuticals. Clinical trials
Phase III results on advanced renal cell carcinoma suggested a 30% or 3 months improvement in median progression-free survival compared to sorafenib but showed an inferior overall survival rate of the experimental arm versus the control arm. The Food and Drug Administrations Oncologic Drugs Advisory Committee voted in May 2013 13 to 1 against recommending approval of tivozanib for renal cell carcinoma.
Micrognathism is a condition where the jaw is undersized. It is also sometimes called mandibular hypoplasia. It is common in infants, but is usually self-corrected during growth, due to the jaws increasing in size. It may be a cause of abnormal tooth alignment and in severe cases can hamper feeding. It can also, both in adults and children, make intubation difficult, either during anesthesia or in emergency situations. Causes
While not always pathological, it can present as a birth defect in multiple syndromes including:

Catel–Manzke syndrome
Bloom syndrome
Coffin–Lowry syndrome
Congenital rubella syndrome
Cri du chat syndrome
DiGeorge syndrome
Ehlers–Danlos syndrome
Fetal alcohol syndrome
Hallermann–Streiff syndrome
Hemifacial microsomia (as part of Goldenhar syndrome)
Incontinentia pigmenti
Juvenile idiopathic arthritis
Marfan syndrome
Möbius syndrome
Noonan syndrome
Pierre Robin syndrome
Prader–Willi syndrome
Progeria
Silver–Russell syndrome
Seckel syndrome
Smith–Lemli–Opitz syndrome
Stickler syndrome
Treacher Collins syndrome
Trisomy 13 (Patau syndrome)
Trisomy 18 (Edwards syndrome)
Trisomy 21 (Down syndrome)
Wolf–Hirschhorn syndrome
X0 syndrome (Turner syndrome)

Diagnosis
It can be detected by the naked eye as well as dental or skull X-Ray testing. Treatments
Micrognathia can be treated by surgery, orthodontic braces, and modified eating methods. Early detection of the problem and monitoring as the problems grows can help understand it better and find the most effective treatment procedure. See also
Human mandible
Macrognathism
Retrognathism

References
External links

"Micrognathia". Medline Plus. 12 May 2009. Retrieved 21 May 2011.