Name | Caspofungin |
Synonyms | CS-1171 Aids058650 Aids-058650 PneuMocandin B0,1-[(4R,5S)-5-[(2-aMinoethyl)aMino]-N2-(10,12-diMethyl-1-oxotetradecyl)-4-hydroxy-L-ornithine]-5-[(3R)-3-hydroxy-L-ornithine]- |
CAS | 162808-62-0 |
EINECS | 1806241-263-5 |
InChI | InChI=1/C52H88N10O15/c1-5-28(2)24-29(3)12-10-8-6-7-9-11-13-39(69)56-34-26-38(68)46(55-22-21-54)60-50(75)43-37(67)19-23-61(43)52(77)41(36(66)18-20-53)58-49(74)42(45(71)44(70)31-14-16-32(64)17-15-31)59-48(73)35-25-33(65)27-62(35)51(76)40(30(4)63)57-47(34)72/h14-17,28-30,33-38,40-46,55,63-68,70-71H,5-13,18-27,53-54H2,1-4H3,(H,56,69)(H,57,72)(H,58,74)(H,59,73)(H,60,75)/t28?,29?,30-,33-,34+,35+,36-,37+,38-,40?,41+,42?,43+,44+,45+,46-/m1/s1 |
Molecular Formula | C52H88N10O15 |
Molar Mass | 1093.31 |
Density | 1.36±0.1 g/cm3(Predicted) |
Boling Point | 1408.1±65.0 °C(Predicted) |
Flash Point | 805.4°C |
Vapor Presure | 0mmHg at 25°C |
pKa | 9.86±0.26(Predicted) |
Refractive Index | 1.623 |
Physical and Chemical Properties | Caspofungin was the first echinocandin approved for the treatment of invasive fungal infections. In vitro and in vivo experiments confirmed that caspofungin had good antibacterial activity against important opportunistic infection pathogens-Candida and Aspergillus. Caspofungin ruptures the cell wall by inhibiting the synthesis of 1, 3-β-glucan. Caspofungin has been clinically shown to be effective in the treatment of various candidiasis and aspergillosis. |
product features | caspofungin is a semi-synthetic lipopeptide (echinocandin, echinocandin) compound synthesized from Glarea Lozoyensis fermentation products. Caspofungin acetate inhibits the synthesis of β(1,3)-D-glucan, an essential component of the cell wall of many filamentous fungi and yeasts. β(1,3)-D-glucan is absent in the cells of mammals. In vitro pharmacological studies have shown that caspofungin has antibacterial activity against many pathogenic Aspergillus and Candida fungi. |
mechanism of action | (1,3)- D-glucan synthase is a key component of fungal cell wall synthesis, and caspofungin can inhibit the enzyme non-competitively Play an antifungal effect. After intravenous administration, the plasma drug concentration decreases rapidly due to tissue distribution, and the drug is gradually re-released from the tissue. The metabolism of caspofungin increases with the increase of dose, and there is a dose correlation in the time to reach steady state after multiple administration. Therefore, in order to achieve an effective therapeutic level and avoid drug accumulation, a loading dose should be given for the first time, followed by a maintenance dose. When cytochrome p450 3A4 inducers are used simultaneously, such as rifampicin, carbamazepine, dexamethasone, phenytoin, etc., it is recommended to increase the maintenance dose of caspofungin. |
indications | indications of FDA-approved carpofungin include: 1. fever with neutropenia: it is defined as fever> 38 ℃, with absolute neutrophil count (ANC)≤ 500/ml, or with ANC ≤ 1000/ml, and it is predicted that the minimum can be reduced to below 500/ml. According to the American Infectious Diseases Association (IDSA), although patients with persistent fever and neutropenia have been treated with broad-spectrum antibiotics, empirical antifungal therapy is still recommended for high-risk patients. These antifungal drugs include caspofungin. 2. Invasive candidiasis: IDSA recommends echinocandins (such as caspofungin) as the first choice for candidemia. It can also be used to treat abdominal abscess, peritonitis and thoracic infection caused by candida infection. 3. esophageal candidiasis: caspofungin can be used to treat esophageal candidiasis in patients with refractory or other therapeutic intolerance. Several studies have found that the therapeutic effect of caspofungin is comparable to that of fluconazole. In 2002, Villanova et al. conducted a double-blind randomized trial on 177 HIV patients diagnosed with esophageal candidiasis. The researchers randomly divided the patients into two groups: the caspofingin group (50mg intravenous) or the fluconazole group (200mg intravenous) once a day for 7-21 days. At 5-7 days after discontinuation, the symptoms were relieved and the endoscopy improved significantly. The effective rates of the two groups were 81% and 85% respectively. In the same year, the retrospective analysis of Kartsonis et al. confirmed the efficacy of cabofengin on fluconazole-resistant or refractory esophageal candidiasis. In 14 patients with in vitro test resistance, 11 cases were successful, and in 11 cases Of the refractory patients, 7 cases were successful. 4. Invasive aspergillosis: Caspofungin has been approved for the treatment of invasive aspergillosis in patients with intolerance, drug resistance and inefficacy of the main antifungal drug voriconazole. But echinocandin is not recommended as a first-line treatment. |
production process | caspofungin needs to be prepared by fermentation semi-synthesis technology. it needs to first obtain the crude product of the main ring through fermentation technology, then obtain the intermediate product through separation and purification, then use the intermediate product as the starting material, and use the synthesis technology to complete the side chain splicing, and finally obtain the target component. Because "fermented semi-synthetic" products need to undergo multiple technical links such as fermentation, separation and purification, synthesis, etc., the technical route and process parameter control are very complicated. In addition, the regulatory requirements for the application and registration of a fermented semi-synthetic product such as Capofinjing are also extremely high. The application documents need to start from the source of fermentation. It is not only necessary to systematically study the strain cultivation, fermentation process, and purification process, but also to explore the route and conditions of the synthesis link, and to control impurities in the process. Because the final product is quite fragile, all previous efforts will be wasted if it is not careful. The technical difficulty and cost are not small. According to the information approved by Hengrui's previous announcement, the research and development investment in this variety is 30.54 million yuan. It is precisely because of the high technical barriers and the good competitive landscape that Hengrica Bofen has maintained a relatively good price space after its listing. Judging from the winning bid, Mercadon 50mg and 75mg have more than 20 winning bid areas, and the median winning price is 1734.96 yuan/branch and 2277.08 yuan/branch respectively. Hengrui 50mg specification has covered 15 regions after listing, and the median winning price is 1449.67 yuan/branch. |
market situation | kapofen is a lipopeptide compound developed by Mercadon through fermentation semi-synthetic technology, which can inhibit the synthesis of β(1,3)-D-glucan, the basic component of many filamentous fungi and yeast cell walls, thus playing an antifungal role. 2001/01/26 was approved by FDA for listing, becoming the world's first approved echinococcus antifungal agent. 2002/09/24 Approved for listing in China under the trade name Cossez. caspofungin is currently an antifungal infection drug recommended by clinical guidelines in various countries. For example, the guidelines issued by the American Society for Infectious Diseases (IDSA) in December 2015 recommend the use of echinococcin drugs (such as caspofungin) instead of fluconazole as a first-line drug to treat candidemia. The "Guidelines for the Diagnosis and Treatment of Invasive Fungal Infection in Severe Patients" formulated by the Critical Care Medicine Branch of the Chinese Medical Association also recommends caspofungin as a preventive drug for invasive fungal infection and target treatment after infection. The sales performance of Capoffine Net after its listing was very stable. The patent protection expired in 2014. Since then, the sales volume has gradually declined, and the sales volume in 2018 was 0.326 billion US dollars. Carpofun.com 2010-2018 Global Sales (Million USD) |
adverse reactions | since (1,3)- D-glucan in fungal cell wall does not exist in mammalian cells, the incidence of adverse reactions of caspofungin is relatively low. Common adverse reactions include fever, chills, phlebitis, thrombophlebitis, celiac disease, nausea, vomiting, rash, headache, abdominal pain and diarrhea. There are also reports of elevated transaminase after the use of caspofungin, mainly due to the slow metabolism of the drug in the liver. |
toxic substance data | information provided by: pubchem.ncbi.nlm.nih.gov (external link) |