Pathways

Voriconazole is an triazole antifungal medication used to treat serious, invasive fungal infections. It has increased affinity to 14-alpha sterol demethylase which means it is useful against Fluconazole-resistant organisms. Voriconazole is taken either orally or injected intravenously. The bioavailability of voriconazole is 96%. When taken orally it is transported from the intestine into the intestinal epithelial cell possibly via solute carrier family 15 member 1, one of 3 drug transporters into epithelial cells. It is then transported into blood vessels via ATP-binding cassette sub-family C member 3. It is then transported through the blood to the liver where it is transported in by a liver drug transporter like solute carrier family 22 member 1. On the endoplasmic reticulum membrane Voriconazole is metabolized into Voriconazole N-Oxide by Cytochrome P450 2C9, Cytochrome P450 2C19, Cytochrome P450 3A4, Cytochrome P450 3A5, or Cytochrome P450 3A7, which makes up 72% of metabolites found. Voriconazole N-Oxide is metabolized into a voriconazole related compound (UK-51,060) by an unknown enzyme. That is predicted by biotransformer to be metabolized by Carbonyl reductase [NADPH] 1 into a similar voriconazole related compound (UK-215,364). That is predicted by biotransformer to be metabolized by UDP-glucuronosyltransferase 1-3 into Voriconazole O-glucuronide derivative (1). Voriconazole also metabolizes into 4-Hydroxyvoriconazole via the enzymes Cytochrome P450 3A4, Cytochrome P450 3A5, or Cytochrome P450 3A7. 4-Hydroxyvoriconazole is predicted by biotransformer to be metabolized by UDP-glucuronosyltransferase 1-3 into 4-Hydroxyvoriconazole 4-O-glucuronide. Voriconazole and all the metabolites are transported out of the liver and into blood vessels by a transport protein such as multidrug resistance-associated protein 4. They all then travel to the kidney where they are excreted in the urine. Less than 2% of the dose is excreted as unchanged voriconazole. 72% is excreted as the metabolite voriconazole N-oxide.

Voriconazole is a triazole antifungal agent used to treat invasive fungal infections, generally seen in patients who are immunocompromised. It has an increased affinity to 14-alpha sterol demethylase, and therefore makes it useful against fluconazole-resistant fungal infections. It is taken orally and used to treat esophageal candidiasis, cadidemia, invasive pulmonary aspergillosis, and serious fungal infections caused by Scedosporium apiospermum and Fusarium spp. Voriconazole is effective against all Candida species (including those resistant to other antifungal drugs), Cryptococcus neoformans, Trichosporon beigelii, and Saccharomyces cerevisiae. Voriconazole inhibits and antagonizes the production of ergosterol by inhibiting Lanosterol 14-alpha demethylase. It has a higher affinity for Lanosterol 14-alpha demethylase than other antifungal agents. Lanosterol 14-alpha demethylase is the enzyme that catalyzes the synthesis of 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol from lanosterol. With this enzyme inhibited ergosterol synthesis cannot occur which causes a significant low concentration of ergosterol in the fungal cell. Ergosterol is essential in maintaining membrane integrity in fungi. Without ergosterol, the fungus cell cannot synthesize membranes thereby increasing fluidity and preventing growth of new cells. With fungal growth limited, it allows the immune system to destroy the fungal cells.

Vorapaxar also known as Zontivity, is an inhibitor for platelet aggregation used to treat patients with a history of myocardial infarction or peripheral arterial disease to reduce the chance of thrombotic cardiovascular events. Vorapaxar inhibits protease-activated receptor 1 (PAR-1), which is a G protein-coupled receptor that is expressed on the platelet. Inhibition of PAR-1 prevents platelet aggregation and activation. Vorapaxar is administered orally and rapidly absorbs and travels through the bloodstream. It is metabolized to major metabolites M20 and M19 by CYP3A4 and CYP2J2. This is then eliminated primarily through feces and urine. Due to the anticoagulant and antiplatelet nature, herbs and supplements with similar activity should be avoided such as garlic, ginger, bilberry, danshen, piracetam and ginkgo biloba. St.John's Wort should also be avoided as it induces CYP3A metabolism and will reduce the concentration of Vorapaxar. Caution should be exercised with grapefruit products, as coadministration with strong inhibitors should be avoided.

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

Vitamin K describes a group of lipophilic, hydrophobic vitamins that exist naturally in two forms (and synthetically in three others): vitamin K1, which is found in plants, and vitamin K2, which is synthesized by bacteria. Vitamin K is an important dietary component because it is necessary as a cofacter in the activation of vitamin K dependent proteins. Metabolism of vitamin K occurs mainly in the liver. In the first step, vitamin K is reduced to its quinone form by a quinone reductase such as NAD(P)H dehydrogenase. Reduced vitamin K is the form required to convert vitamin K dependent protein precursors to their active states. It acts as a cofactor to the integral membrane enzyme vitamin K-dependent gamma-carboxylase (along with water and carbon dioxide as co-substrates), which carboxylates glutamyl residues to gamma-carboxy-glutamic acid residues on certain proteins, activating them. Each converted glutamyl residue produces a molecule of vitamin K epoxide, and certain proteins may have more than one residue requiring carboxylation. To complete the cycle, the vitamin K epoxide is returned to vitamin K via the vitamin K epoxide reductase enzyme, also an integral membrane protein. The vitamin K dependent proteins include a number of important coagulation factors, such as prothrombin. Thus, warfarin and other coumarin drugs act as anticoagulants by blocking vitamin K epoxide reductase.