Pathways

Rose bengal I-131 is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Rose bengal I-131 passes through the liver and is then excreted from the body mainly through the kidney.

Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is extensively metabolized in the liver by the cytochrome p450 enzymes CYP2C8 and CYP2C9 to para-hydroxy rosiglitazon, ortho-hydroxy rosiglitazone and N-desmethyl rosiglitazone. N-desmethyl rosiglitazone is the major metabolite and is further metabolized to N-desmethyl-p-hydroxyrosiglitazone, N-desmethyl glucuronide rosiglitazone and N-desmethyl-O-hydroxy rosiglitazone. Both para-hydroxy rosiglitazon and ortho-hydroxy rosiglitazone are excreted as sulfated or glucuronidated metabolites.

Statins are a class of medications that lower lipid levels and are administered to reduce illness and mortality in people who are at high risk of cardiovascular disease. Rosuvastatin is a well-tolerated orally-administered synthetic statin that reduces total cholesterol levels, low-density lipoprotein (LDL)-cholesterol, triglyceride, and very-low-density lipoprotein (VLDL)-cholesterol. It also increases levels of high-density lipoprotein (HDL)-cholesterol. It reduces cholesterol biosynthesis due to the result of a prolonged duration of HMG-CoA reductase inhibition. Reported side effects of Rosuvastatin include constipation, flatulence, dyspepsia (indigestion), abdominal pain, headache, and myalgia (muscle pain). The primary therapeutic mechanism of action of statins is the inhibition of the rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase in hepatocytes. HMG-CoA reductase catalyzes the conversion of HMG-CoA into mevalonic acid, a precursor for cholesterol biosynthesis. Statins bind reversibly to the active site of HMG-CoA reductase and the subsequent structural change in the enzyme effectively disables it. Due to the resulting decrease in intracellular sterol levels, the ER membrane protein INSIG no longer binds to SREBP cleavage-activating protein (SCAP) which is, itself, bound to the transcription factor sterol regulatory element-binding protein (SREBP). Freed from INSIG, SCAP escorts SREBP to the Golgi apparatus from the ER as cargo in COPII vesicles. At the Golgi membrane, two proteases, S1P and S2P, sequentially cleave the SCAP-SREBP complex, releasing the mature form of SREBP into the cytoplasm. SREBP then translocates to the nucleus where it is transported into the nucleoplasm by binding directly to importin beta in the absence of importin alpha. SREBP binds to the sterol regulatory element (SRE) present in the promoter region of genes involved in cholesterol uptake and cholesterol synthesis, including the gene encoding the low-density lipoprotein (LDL) receptor (LDL-R). As a result, LDL-R gene transcription increases which then leads to an increased synthesis of the LDL-R protein. LDL-R localizes to the endoplasmic reticulum for transport and exocytosis to the cell surface. The elevated amount of LDL-R results in more circulating free LDL cholesterol binding and subsequent internalization via endocytosis. Lysosomal degradation of the internalized LDL cholesterol elevates cellular cholesterol levels to maintain homeostasis. This drug is administered as an oral tablet.

Rosuvastatin, sold as Crestor, Rosulip and Zuvamor, belongs to the class of drugs known as statins. It is taken orally to inhibit the endogenous production of cholesterol in the liver. Statins do this by inhibiting the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme is typically responsible for the conversion of HMG-CoA to mevalonic acid, the third and rate-limiting step of cholesterol, LDL and VLDL synthesis. Rosuvastatin has a similar structure to 3-hydroxy-3-methylglutaryl-CoA, and acts to competitively inhibit the action of HMG-CoA reductase. Statins such as rosuvastatin are used to lower the risk of cardiovascular disease due to higher than normal levels of LDL ad VLDL, which are sometimes known as bad cholesterol. Cardiovascular disease can include heart attacks, angina, strokes and artery disease, and LDL and VLDL levels are a risk factor for its development. Because rosuvastatin is not highly metabolized by Cytochrome P450 enzymes and is taken up quickly due to its hydrophilicity, it has less drug interactions than other statins. It is also the most potent statin, meaning a smaller dose is required. However, it does not prevent CVD any better than other statins.

Metabolites of Rosuvastatin are predicted with biotransformer.

Rotigotine is an agonist at all 5 dopamine receptor subtypes (D1-D5) but binds to the D3 receptor with the highest affinity. It is delivered continuously through the skin (transdermal) using a silicone-based patch that is replaced every 24 hours.