Pharmacokinetic results of a phase I trial of sorafenib in combination with dacarbazine in patients with advanced solid tumors was written by Brendel, Erich;Ludwig, Matthias;Lathia, Chetan;Robert, Caroline;Ropert, Stanislas;Soria, Jean-Charles;Armand, Jean-Pierre. And the article was included in Cancer Chemotherapy and Pharmacology in 2011.Name: 1H-Imidazole-4-carboxamide This article mentions the following:
Sorafenib, a multikinase inhibitor of Raf and several growth factor receptors, is under investigation in combination with dacarbazine, a commonly used chemotherapeutic agent for the treatment of many cancers. The current phase I study investigates the effects of sorafenib on the pharmacokinetic (PK) profile of dacarbazine and its metabolite 5-amino-imidazole-4-carboxamide (AIC). AIC is formed in amounts equimolar to the active alkylating moiety, methane diazohydroxide, which is undetectable by known validated assays. Patients with advanced solid tumors received i.v. dacarbazine 1000 mg/m2 on day 1 of a 21-day cycle to evaluate the PK of dacarbazine alone. Sorafenib 400 mg was administered twice daily continuously starting at day 2 of cycle 1. The PK of dacarbazine in the presence of sorafenib was assessed on day 1 of cycle 2. Sorafenib PK was also assessed at steady state. PK data were available for 15 of 23 patients. With concomitant administration of sorafenib, the mean AUC and C max values of dacarbazine were reduced by 23% and 16%, resp. Mean AUC and C max values of AIC were increased by 41% and 45%, resp., with individual increases of up to 106% and 136%, resp. The apparent terminal half-lives of the two compounds were not significantly influenced by sorafenib. Based on coefficients of variation, the AUC and C max values for sorafenib and its three metabolites were highly variable with dacarbazine coadministration. Concomitant administration of sorafenib and dacarbazine as described above may result in decreased dacarbazine exposure but increased AIC exposure. In the experiment, the researchers used many compounds, for example, 1H-Imidazole-4-carboxamide (cas: 26832-08-6Name: 1H-Imidazole-4-carboxamide).
1H-Imidazole-4-carboxamide (cas: 26832-08-6) belongs to imidazole derivatives. Imidazole is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole is incorporated into many important biological compounds. The most pervasive is the amino acid histidine, which has an imidazole side-chain. Histidine is present in many proteins and enzymes, e.g. by binding metal cofactors, as seen in hemoglobin.Name: 1H-Imidazole-4-carboxamide
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem