They cross the blood–brain barrier and enter the brain, where they most concentrated at the thalamus, basal ganglia, midbrain, and cingulate gyrus.Selegiline is mostly metabolized in the intestines and liver; it and its metabolites are excreted in the urine.Buccal administration of selegiline results in 5-fold higher bioavailability, more reproducible blood concentration, and produces less amphetamine metabolites than the oral tablet form. Metabolism
Selegiline is metabolized by cytochrome P450 to L-desmethylselegiline and levomethamphetamine. Desmethylselegiline has some activity against MAO-B, but much less than that of selegiline. It is thought to be further metabolized by CYP2C19. Levomethamphetamine (the less potent of the two enantiomers of methamphetamine) is converted to levoamphetamine (the less potent of the two enantiomers of amphetamine, with regards to psychological effects). Due to the presence of these metabolites, people taking selegiline may test positive for "amphetamine" or "methamphetamine" on drug screening tests. While the amphetamine metabolites may contribute to selegilines ability to inhibit reuptake of the neurotransmitters dopamine and norepinephrine, they have also been associated with orthostatic hypotension and hallucinations. The amphetamine metabolites are hydroxylated and, in phase II, conjugated by glucuronyltransferase. A newer anti-Parkinson MAO-B inhibitor, rasagiline, metabolizes into 1(R)-aminoindan, which has no amphetamine-like characteristics. Patch
Following application of the patch to humans, an average of 25% to 30% of the selegiline content is delivered systemically over 24 hours.
In either case, "fusion-negative" alveolar rhabdomyosarcoma have similar clinical presentation and outcome as embryonal rhabdomyosarcoma, thus risk stratification, prognosis, and treatment intensity of rhabdomyosarcoma are now determined by fusion-status instead of histological classification. Imaging
After a physical exam, formal diagnosis of RMS in adult patients requires a computed tomography (CT) scan, which can assess the areas affected and to delineate the tumor. In children, physicians may opt for magnetic resonance imaging (MRI) to limit radiation exposure in younger populations. In the majority of individuals diagnosed with rhabdomyosarcoma, more than half are diagnosed before the age of 10. Prognosis
The prognosis for rhabdomyosarcoma has improved greatly in recent decades, with over 70% of people surviving for five years after diagnosis. The combined use of radiotherapy and surgery has significantly reduced the mortality rates compared to patients who did not undergo any radiotherpay or chemotherapy treatments. Embryonal rhabdomyosarcoma is generally associated with better prognosis than alveolar rhabdomyosarcoma, with a 5-year survival prognosis of 82% and 53%, respectively. This may be due to the more aggressive and metastatic nature of ARMS that can be attributed to its PAX3–FOXO1 or PAX7–FOXO1 gene fusions. Nevertheless, some embryonal rhabdomyosarcoma patients with a rare Leu122Arg mutation in MYOD1 gene have a very poor outcome. In two different studies, none of the subjects with the MYOD1 mutation survived. Tumors due to this mutation commonly manifest in the head and neck area, causing the mutated protein to behave like an oncogene.There have not been many studies linking the genetic profile and clinical outcome of ERMS.