Pathways

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

Metabolites of Cyclopentolate are predicted with biotransformer.

Cyclophosphamide is an alkylating agent used in the treatment of certain cancers. Following absorption, cyclophosphamide is converted into 4-hydroxyphosphamide by a variety of cytochrome P450 isozymes in the liver. 4-Hydroxyphosphamide is more soluble than cyclophosphamide and is the primary form of the drug that is transported in blood. 4-Hydroxyphosphamide crosses the plasma membrane of the cancer cell and spontaneuosly forms aldophosphamide. This is a reversible reaction. Aldophosphamide can decompose into acrolein and phosphoramide mustard. Phosphoramide mustard is the active alkylating agent and forms alkyl adducts with DNA through a phosphoramide aziridinium intermediate. Alkylation of DNA causes DNA damage and eventually cell death.

Cyclophosphamide is an antineoplastic alkylating agent used to treat lymphoma and leukemia. Cyclophosphamide is either injected or taken orally to enter the blood where it travels to the liver in order to be activated by various enzymes and cytochrome p450 isoforms (2A6, 2B6, 3A4, 2C9, 2C18, 2C19) eventually into aldophosphamide. Aldophosphamide is released into the bloodstream through Golgi apparatus vesicles. Aldophosphamide is then taken up by cancer cells into the cytosol where it is then degraded into acrolein and carboxyphosphamide but more importantly it turns into phosphoramide mustard, the main cytotoxic agent. Phosphoramide mustard carries out its cytotoxic events in three different ways. Firstly, it alkylates DNA bases resulting in the DNA becoming fragmented by repair enzymes trying to replace the alkylated bases with new ones. This prevents DNA synthesis and RNA transcription as the DNA is damaged and cannot be read properly. Phosphoramide mustard also works by creating crosslinks between DNA bases preventing DNA from being "unzipped" for replication or transcription. Lastly, phosphoramide mustard works by inducing the misfiring of nucleotides leading to single nucleotide polymorphisms that can possibly cause larger-scale problems in mutations. All three mechanisms of phosphoramide mustard inhibit cellular survival through replication and RNA synthesis, effectively killing the cancer cell. Because the metabolism of cyclophosphamide is linked with the production of the active cytotoxic agent, cyclophosphamide induces its own metabolism with results in an increase in blood plasma clearance (short half-lives). Cyclophosphamide also can cause adverse effects such as alopecia (spot baldness), sterility, birth defects, mutations, and other types of cancer. It is administered as an intravenous injection or an oral tablet.

Cyclophosphamide is an alkylating agent used in the treatment of certain cancers. Following absorption, cyclophosphamide is converted into 4-hydroxyphosphamide by a variety of cytochrome P450 isozymes in the liver. 4-Hydroxyphosphamide is more soluble than cyclophosphamide and is the primary form of the drug that is transported in blood. 4-Hydroxyphosphamide crosses the plasma membrane of the cancer cell and spontaneuosly forms aldophosphamide. This is a reversible reaction. Aldophosphamide can decompose into acrolein and phosphoramide mustard. Phosphoramide mustard is the active alkylating agent and forms alkyl adducts with DNA through a phosphoramide aziridinium intermediate. Alkylation of DNA causes DNA damage and eventually cell death.