吡喹酮
吡喹酮（英语：Praziquantel，或英语：Biltricide）为一种用于人类及动物的驱虫药，专门治疗绦虫及吸虫。对于血吸虫、中华肝吸虫、广节裂头绦虫特别有效，吡喹酮为世界卫生组织基本药物标准清单上的药物，为世界上对于基本公共卫生最重要的药物之一。[1]1970年代由拜耳公司的药学部研发成功。
 | |
 | |
| 临床资料 | |
|---|---|
| 商品名 | Biltricide |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a608048 |
| 怀孕分级 |
|
| 给药途径 | oral |
| ATC码 | |
| 法律规范状态 | |
| 法律规范 |
|
| 药物动力学数据 | |
| 生物利用度 | relatively small |
| 药物代谢 | hepatic |
| 生物半衰期 | 0.8 to 1.5 hours (Main Metabolites 4 to 5 hours) |
| 排泄途径 | mainly in urine |
| 识别信息 | |
| |
| CAS号 | 55268-74-1  |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.054.126 |
| 化学信息 | |
| 化学式 | C19H24N2O2 |
| 摩尔质量 | 312.411 |
| 3D模型（JSmol） | |
| |
| |
医疗用途
吡喹酮可以用于治疗人类、哺乳类，以及鱼类的寄生虫病。包含肠胃道或是外部的感染，以下为其适用疾病：
- Feline taeniasis caused in cats by gastrointestinal infection with adult tapeworms of the species Taenia taeniaeformis; used either alone or in combination with pyrantel pamoate
- Toxocariasis in cats and dogs whose gut is infected with the roundworms/nematodes Toxocara cati or Toxocara canis, respectively; use is often combined with pyrantel [3]
- Schistosomiasis caused by trematodes of the genus Schistosoma.[4]As of 2005, praziquantel is the primary treatment for human schistosomiasis, for which it is usually effective in a single dose.[5]
- Clonorchiasis brought on by the Chinese liver fluke Clonorchis sinensis[6]
- Paragonimiasis caused by infection with lung flukes, mostly of the species Paragonimus westermani[来源请求]
- Fasciolopsiasis caused by intestinal fluke Fasciolopsis buski[7]
- Diplozoon paradoxum and other Trematoda infections of many fish species[8]
副作用
The majority of side effects develop due to the release of the contents of the parasites as they are killed and the consequent host immune reaction. The heavier the parasite burden, the heavier and more frequent the side effects normally are.
- Central nervous system: Frequently occurring side effects are dizziness, headache, and malaise. Drowsiness, somnolence, fatigue, and vertigo have also been seen. Almost all patients with cerebral cysticercosis experience CNS side effects related to the cell-death of the parasites (headache, worsening of pre-existing neurological problems, seizures, arachnoiditis, and meningism). These side effects may be life-threatening and can be reduced by coadministration of corticosteroids. It is strongly recommended that all patients with cerebral cysticercosis are hospitalized during treatment.
- GI Tract: Approximately 90% of all patients have abdominal pain or cramps with or without nausea and vomiting. Diarrhea may develop and may be severe with colic. Sweating, fever, and sometimes bloody stools may occur together with diarrhea.
- Liver: Asymptomatic and transient increases of liver enzymes (AST and ALT) are noted frequently (up to 27%). No case of symptomatic liver damage has ever been seen so far.
- Sensitivity reactions: Urticaria, rash, pruritus and eosinophilia in white blood cell counts
- Other locations/body as a whole: Lower back pain, myalgia, arthralgia, fever, sweating, various cardiac arrhythmias, and hypotension
Drug interactions
The antibiotic rifampicin decreases plasma concentrations of praziquantel.[9]
Carbamazepine and phenytoin are reported to reduce the bioavailability of praziquantel.[10]
Chloroquine reduces the bioavailability of praziquantel.[11]
The drug cimetidine heightens praziquantel bioavailability.[12][13]
Mechanism of action
The mode of action is not exactly known at present, but experimental evidence indicates praziquantel increases the permeability of the membranes of schistosome cells towards calcium ions. The drug thereby induces contraction of the parasites, resulting in paralysis in the contracted state. The dying parasites are dislodged from their site of action in the host organism and may enter systemic circulation or may be destroyed by host immune reaction (phagocytosis). Additional mechanisms including focal disintegrations and disturbances of oviposition (laying of eggs) are seen in other types of sensitive parasites.
Another hypothesis concerning the mechanism of action of praziquantel has been recently reported. The drug seems to interfere with adenosine uptake in cultured worms. This effect may have therapeutical relevance given that the schistosome, as the Taenia and the Echinococcus (other praziquantel-sensitive parasites), is unable to synthesize purines such as adenosine de novo.
Bayer's Animal Health Division website states, "Praziquantel is active against cestodes (tapeworms). Praziquantel is absorbed, metabolized in the liver, and excreted in the bile. Upon entering the digestive tract from the bile, cestocidal activity is exhibited. Following exposure to praziquantel, the tapeworm loses its ability to resist digestion by the mammalian host. Because of this, whole tapeworms, including the scolices (plural of "scolex"), are very rarely passed after administration of praziquantel. In many instances, only disintegrated and partially digested pieces of tapeworms will be seen in the stool. The majority of tapeworms are digested and are not found in the feces."[14]
Praziquantel is administered as a racemate, but only the (R)-enantiomer is biologically active; the enantiomers may be separated using a resolution of an amine obtained from praziquantel.[15]
Pharmacokinetics
Praziquantel is well absorbed (about 80%) from the gastrointestinal tract. However, due to extensive first-pass metabolism, only a relatively small amount enters systemic circulation. Praziquantel has a serum half-life of 0.8 to 1.5 hours in adults with normal renal and liver function. Metabolites have a half-life of 4 to 5 hours. In patients with significantly impaired liver function (Child Pugh classes B ll///d C), the serum half-life is increased to 3 to 8 hours. Praziquantel and its metabolites are mainly excreted renally; within 24 hours after a single oral dose, 70 to 80% is found in urine, but less than 0.1% as the unchanged drug. Praziquantel is metabolized through the cytochrome P450 pathway via CYP3A4. Agents that induce or inhibit CYP3A4 such as phenytoin, rifampin, and azole antifungals will affect the metabolism of praziquantel.
Praziquantel has a particularly dramatic effect on patients with schistosomiasis. Studies of those treated have shown that within six months of receiving a dose of praziquantel, up to 90% of the damage done to internal organs due to schistosomiasis infection can be reversed.[5]
History
Praziquantel was developed in the laboratories for parasitological research of Bayer AG and Merck KGaA in Germany (Elberfeld and Darmstadt) in the mid 1970s.
商品名
- Biltricide (Bayer) 600 mg Tablets：人类使用
- Cesol (Merck) Tablets
- Cestoved (Vedco) ：药片或注射剂，兽医使用
- Cysticide (Merck) Tablets
- Distocide (Shin Poong Pharm. Co. Ltd) 600mg tablet：人类使用
- Distoside (Chandra Bhagat Pharma Pvt Ltd) 600mg tablet：人类使用
- Droncit (Bayer) ：兽医使用
- Drontal (combination with pyrantel pamoate) (Bayer)：兽医使用
- D-Worm (Farnum) for veterinary use; note that D-Worm also makes roundworm medicine containing piperidine which is not effective against tapeworms.
- Fish Tapes (Thomas Labs) for aquarium use
- Kaicide (Taiwan)
- Milbemax (combination with milbemycin oxime) (Novartis)：兽医使用
- Popantel (Jurox)
- PraziPro (Hikari) ：水生动物饲养使用
- Praz-Tastic (NFP/National Fish Pharmaceuticals) ：水生动物饲养使用
- Pure Prazi (COTS Koi/Children of the Sun Koi)：水生动物饲养使用
- PraziPure (J.K.O., Inc. d/b/a Kodama Koi Farm & Kodama Koi Garden; licensed by COTS Koi)：水生动物饲养使用
- Profender (combination with emodepside) (Bayer) ：兽医使用
- Tape Worm Tabs (Trade Winds) ：兽医使用
- Zentozide (Berich (Thailand) Co)
核准状况
吡喹酮名列世界卫生组织基本药物标准清单之中，是世界上对于基本公共卫生最重要的药物之一。[1]
在英国，吡喹酮并未获准在人体上使用。但在必要时可以根据在患者实名的情况下进口。[16]在英国吡喹酮可以作为兽用驱虫药销售。
在美国，吡喹酮被FDA批准用于血吸虫病及肝吸虫病的治疗，尽管它对其他种类的感染也有效。[17]
参考文献
- ^ 1.0 1.1 WHO Model List of EssentialMedicines (PDF). World Health Organization. October 2013 [22 April 2014]. （原始内容存档 (PDF)于2014-04-23）.
- ^ Matthaiou DK, Panos G, Adamidi ES, Falagas ME. Carabin, Hélène , 编. Albendazole versus Praziquantel in the Treatment of Neurocysticercosis: A Meta-analysis of Comparative Trials. PLoS Negl Trop Dis. 2008, 2 (3): e194 [2015-06-18]. PMC 2265431
. PMID 18335068. doi:10.1371/journal.pntd.0000194. （原始内容存档于2009-02-02）.
- ^ Bowman, Dwight D.; Hendrix, Charles M.; Lindsay, David S.; Barr, Steven C. Feline clinical parasitology First. Ames, Iowa: Iowa State University. 2002: 275. ISBN 0-8138-0333-0. （原始内容存档于2017-09-10）.
- ^ Tchuenté LA, Shaw DJ, Polla L, Cioli D, Vercruysse J. Efficacy of praziquantel against Schistosoma haematobium infection in children. Am. J. Trop. Med. Hyg. December 2004, 71 (6): 778–82 [2015-06-18]. PMID 15642971. （原始内容存档 (PDF)于2020-04-08）.
- ^ 5.0 5.1 The Carter Center. Schistosomiasis Control Program. [2008-07-17]. （原始内容存档于2008-07-20）.
- ^ Shen C, Kim J, Lee JK; et al. Collection of Clonorchis sinensis adult worms from infected humans after praziquantel treatment. The Korean Journal of Parasitology. June 2007, 45 (2): 149–52 [2015-06-18]. PMC 2526309 . PMID 17570980. doi:10.3347/kjp.2007.45.2.149. （原始内容存档于2012-12-20）.
- ^ Mas-Coma S, Bargues MD, Valero MA. Fascioliasis and other plant-borne trematode zoonoses. Int. J. Parasitol. October 2005, 35 (11-12): 1255–78. PMID 16150452. doi:10.1016/j.ijpara.2005.07.010.
- ^ Treatment of fish parasites. 2. Effects of praziquantel, niclosamide, levamisole-HCl, and metrifonate on monogenea (Gyrodactylus aculeati, Diplozoon paradoxum). [2015-06-18]. （原始内容存档于2016-09-22）.
- ^ Ridtitid W, Wongnawa M, Mahatthanatrakul W, Punyo J, Sunbhanich M. Rifampin markedly decreases plasma concentrations of praziquantel in healthy volunteers. Clin. Pharmacol. Ther. November 2002, 72 (5): 505–13. PMID 12426514. doi:10.1067/mcp.2002.129319.
- ^ Quinn DI, Day RO. Drug interactions of clinical importance. An updated guide. Drug Saf. June 1995, 12 (6): 393–452. PMID 8527014. doi:10.2165/00002018-199512060-00005.
- ^ Masimirembwa CM, Naik YS, Hasler JA. The effect of chloroquine on the pharmacokinetics and metabolism of praziquantel in rats and in humans. Biopharm Drug Dispos. January 1994, 15 (1): 33–43. PMID 8161714. doi:10.1002/bdd.2510150103.
- ^ Metwally A, Bennett JL, Botros S, Ebeid F. Effect of cimetidine, bicarbonate and glucose on the bioavailability of different formulations of praziquantel. Arzneimittelforschung. April 1995, 45 (4): 516–8. PMID 7779153.
- ^ Jung H, Medina R, Castro N, Corona T, Sotelo J. Pharmacokinetic study of praziquantel administered alone and in combination with cimetidine in a single-day therapeutic regimen. Antimicrob. Agents Chemother. June 1997, 41 (6): 1256–9. PMC 163896 . PMID 9174180.
- ^ 存档副本. [2015-06-18]. （原始内容存档于2007-05-18）.
- ^ Woelfle, Michael; Seerden, Jean-Paul; de Gooijer, Jesse; Pouwer, Kees; Olliaro, Piero; Todd, Matthew H. Geary, Timothy G. , 编. Resolution of Praziquantel. PLoS Neglected Tropical Diseases (Public Library of Science (PLoS)). 2011-09-20, 5 (9): e1260. ISSN 1935-2735. doi:10.1371/journal.pntd.0001260.
- ^ Antihelmintics - Medicines for Worms; threadword, roundworm. Patient. [2015-06-15]. （原始内容存档于2015-06-18）.
- ^ Brunton, Laurence; Chabner, Bruce; Knollman, Bjorn. Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition 12 edition. New York: McGraw-Hill Education / Medical. 2011-01-10. ISBN 9780071624428.
