| Revision as of 17:36, 20 September 2010 editRjwilmsiBot (talk | contribs)Bots, Pending changes reviewers1,602,950 editsm fixing page range dashes using AWB (7151)← Previous edit |
Latest revision as of 16:24, 12 January 2025 edit undoArthurfragoso (talk | contribs)Extended confirmed users, Template editors4,591 edits dark mode fix |
| (50 intermediate revisions by 33 users not shown) |
| Line 1: |
Line 1: |
|
|
{{short description|Chemical compound}} |
|
{{Drugbox |
|
{{Drugbox |
|
|
| Verifiedfields = changed |
|
| IUPAC_name = 7-chloro-4-propyl] |
|
|
|
| Watchedfields = changed |
|
piperazin-1-yl]quinoline |
|
|
|
| verifiedrevid = 385945861 |
|
| image = Piperaquine.png |
|
|
|
| IUPAC_name = 1,3-bispropane |
|
| alt = |
|
|
|
| image = Piperaquine.png |
|
| CAS_number = 4085-31-8 |
|
|
|
| image_class = skin-invert-image |
|
| ATCvet = |
|
|
|
| alt = |
|
| ATC_prefix = <!-- 'none' if uncategorised --> |
|
|
|
|
|
| ATC_suffix = |
|
|
|
<!--Clinical data--> |
|
| PubChem = 122262 |
|
|
| DrugBank = |
|
| tradename = |
|
|
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
|
| C=29|H=32|Cl=2|N=6 |
|
|
|
| pregnancy_US = <!-- A / B / C / D / X --> |
|
| molecular_weight = 535.51 |
|
|
|
| pregnancy_category = |
|
| smiles = C1CN(CCN1CCCN2CCN(CC2)C3=C4C=CC(=CC4=NC=C3)Cl)C5=C6C=CC(=CC6=NC=C5)Cl |
|
|
|
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
|
| bioavailability = |
|
|
|
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
|
| protein_bound = |
|
|
|
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
|
| metabolism = |
|
|
|
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
|
| elimination_half-life = |
|
|
|
| legal_status = |
|
| excretion = |
|
|
|
| routes_of_administration = |
|
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
|
|
|
|
|
| pregnancy_US = <!-- A / B / C / D / X --> |
|
|
|
<!--Pharmacokinetic data--> |
|
| pregnancy_category= |
|
|
|
| bioavailability = |
|
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
|
|
|
| protein_bound = |
|
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
|
|
|
| metabolism = |
|
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
|
|
|
| elimination_half-life = |
|
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
|
|
|
| excretion = |
|
| legal_status = |
|
|
|
|
|
| routes_of_administration = |
|
|
|
<!--Identifiers--> |
|
|
| CAS_number_Ref = {{cascite|correct|??}} |
|
|
| CAS_number = 4085-31-8 |
|
|
| ATCvet = |
|
|
| ATC_prefix = P01 |
|
|
| ATC_suffix = BF05 |
|
|
| ATC_supplemental = (combination with ]),<br/>{{ATC|P01|BX02}} (combination with ]) |
|
|
| PubChem = 122262 |
|
|
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
|
|
| DrugBank = DB13941 |
|
|
| UNII_Ref = {{fdacite|changed|FDA}} |
|
|
| UNII = A0HV2Q956Y |
|
|
| ChEBI_Ref = {{ebicite|changed|EBI}} |
|
|
| ChEBI = 91231 |
|
|
| ChEMBL_Ref = {{ebicite|changed|EBI}} |
|
|
| ChEMBL = 303933 |
|
|
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
|
|
| ChemSpiderID = 109031 |
|
|
|
|
|
<!--Chemical data--> |
|
|
| C=29 | H=32 | Cl=2 | N=6 |
|
|
| smiles = C1CN(CCN1CCCN2CCN(CC2)C3=C4C=CC(=CC4=NC=C3)Cl)C5=C6C=CC(=CC6=NC=C5)Cl |
|
|
| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
|
|
| StdInChI = 1S/C29H32Cl2N6/c30-22-2-4-24-26(20-22)32-8-6-28(24)36-16-12-34(13-17-36)10-1-11-35-14-18-37(19-15-35)29-7-9-33-27-21-23(31)3-5-25(27)29/h2-9,20-21H,1,10-19H2 |
|
|
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
|
|
| StdInChIKey = UCRHFBCYFMIWHC-UHFFFAOYSA-N |
|
|
| melting_point = 199 |
|
|
| melting_high = 204 |
|
|
| melting_notes = (dec.V |
|
}} |
|
}} |
|
|
|
|
|
|
'''Piperaquine''' is an antiparasitic drug used in combination with ] to treat ]. Piperaquine was developed under the Chinese National Malaria Elimination Programme in the 1960s and was adopted throughout China as a replacement for the structurally similar antimalarial drug chloroquine. Due to widespread parasite resistance to piperaquine, the drug fell out of use as a ], and is instead used as a partner drug for ]. Piperaquine kills parasites by disrupting the detoxification of host ]. |
|
'''Piperaquine''' is an ], a bisquinoline first synthesised in the 1960s, and used extensively in China and Indochina as prophylaxis and treatment during the next 20 years. Usage declined in the 1980s as piperaquine-resistant strains of '']'' arose and artemisinin-based antimalarials became available. However, Chinese scientists discovered that piperaquine was suitable for artemisinin combination therapies (ACTs).<ref>{{cite journal | author=Davis TM, Hung TY, Sim IK, Karunajeewa HA, Ilett KF | title=Piperaquine: a resurgent antimalarial drug | journal=Drugs | year=2005 | volume=65 | issue=1 | pages=75–87 | PMID=15610051 }}</ref> |
|
|
|
|
|
|
|
==Medical uses== |
|
Piperaquine is characterized by slow absorption and a long biological half-life,<ref>{{cite journal | author=D'alessandro U. | title=Progress in the development of piperaquine combinations for the treatment of malaria | journal=Curr Opin Infect Dis | year=2009 | volume=22 | issue=6 | pages=588–92 | PMID=19773652 }}</ref> making it a good partner drug with artemisinin derivatives which are fast acting but have a short biological half-life.<ref>http://apps.who.int/prequal/info_applicants/Guidelines/Nonclinical_Overview_Artemisinin-Derivatives.pdf"</ref> |
|
|
|
Piperaquine is used in combination with ] for the treatment of malaria.<ref name=WHO2015>{{cite book|title=Guidelines for the Treatment of Malaria |edition=3 |publisher=WHO |date=2015 |url=https://www.ncbi.nlm.nih.gov/books/NBK294440/pdf/Bookshelf_NBK294440.pdf |accessdate=22 May 2018 |page=33-34}}</ref> This combination is one of several ] recommended by the World Health Organization for treatment of ].<ref name=WHO2015/> This combination is also recommended by the World Health Organization for treatment of ] after administration of ].<ref name=WHO2015/> |
|
|
|
|
|
|
Piperaquine is also registered for use in some countries in combination with ].<ref name=WHO2015/> However, this combination is not recommended by the World Health Organization due to insufficient data.<ref name=WHO2015/> |
|
Dihydroartemisinin-piperaquine (Eurartesim) was submitted for approval to the ] in 2009.<ref>{{cite web | author = Medicines for Malaria | title = Registration | url = http://www.mmv.org/research-development/project-portfolio/registration | accessdate = 2010-06-20 }}</ref> |
|
|
|
|
|
|
|
==Contraindications== |
|
== References == |
|
|
|
Like ], piperaquine can prolong the ]. Although large randomized clinical trials have not revealed evidence of ], the World Health Organization recommends not using piperaquine in patients with congenital QT prolongation or who are on other ].<ref name=WHO2015/> |
|
{{Reflist}} |
|
|
|
|
|
|
|
==Pharmacology== |
|
{{pharma-stub}} |
|
|
|
===Mechanism of action=== |
|
|
Like chloroquine, piperaquine is thought to function by accumulating in the parasite ] and interfering with the detoxification of ] into ].<ref name=Eastman2009/> |
|
|
|
|
|
===Resistance=== |
|
|
Parasites that survive piperaquine treatment have been increasingly reported since 2010, particularly in Southeast Asia. The epicenter of piperaquine resistance appears to be western ] where in 2014 over 40% of dihydroartemisinin-piperaquine treatments failed to eliminate parasites from the patient's blood.<ref name=Duru2016>{{cite journal|title=''Plasmodium falciparum'' resistance to artemisinin derivatives and piperaquine: a major challenge for malaria elimination in Cambodia |vauthors=Duru V, Witkowski B, Menard D |journal=The American Journal of Tropical Medicine and Hygiene |volume=95 |issue=6 |date=2016 |pages=1228–1238 |doi=10.4269/ajtmh.16-0234|pmc=5154433 |pmid=27928074}}</ref> Characterizing piperaquine-resistant parasites has been technically challenging, as parasites that survive piperaquine treatment in patients appear to remain sensitive to piperaquine ''in vitro''; i.e. piperaquine appears to have the same ] in sensitive parasites and resistant parasites.<ref name=Duru2016/> |
|
|
|
|
|
The mechanism by which parasites become resistant to piperaquine remains unclear. Amplification of the parasite proteases ] and ], both involved in degrading host hemoglobin, is associated with resistance to piperaquine.<ref name=Haldar2018>{{cite journal|title=Drug resistance in ''Plasmodium'' |journal=Nature Reviews Microbiology |date=2018 |vauthors=Haldar K, Bhattacharjee S, Safeukui I |volume=16 |issue=3 |pages=156–170 |doi=10.1038/nrmicro.2017.161|pmc=6371404 |pmid=29355852}}</ref> Similarly, mutations in a gene related to chloroquine resistance, '']'', have been associated with piperaquine resistance; however, parasites that are resistant to chloroquine remain sensitive to piperaquine.<ref name=Haldar2018/><ref name=Duru2016/> In contrast, amplification of the gene for the parasite transporter '']'', a mechanism of parasite resistance to ], is inversely correlated with piperaquine resistance.<ref name=Duru2016/> |
|
|
|
|
|
===Pharmacokinetics=== |
|
|
Piperaquine is a ] drug and therefore is rapidly absorbed and ] across much of the body.<ref name=Eastman2009/> The drug reaches its maximal concentrations approximately 2 hours after administration.<ref name=Eastman2009/> |
|
|
|
|
|
==Chemistry== |
|
|
Piperaquine is available as a base, and as a water-soluble tetraphosphate salt.<ref name=Davis/> |
|
|
|
|
|
==History== |
|
|
Piperaquine was discovered in the 1960s by two separate groups working independently of one another: the ] in China and the ] in France.<ref name=Davis>{{cite journal |vauthors=Davis TM, Hung TY, Sim IK, Karunajeewa HA, Ilett KF | title=Piperaquine: a resurgent antimalarial drug | journal=Drugs | year=2005 | volume=65 | issue=1 | pages=75–87 | pmid=15610051 | doi=10.2165/00003495-200565010-00004}}</ref> In the 1970s and 1980s piperaquine became the primary antimalarial drug of the Chinese National Malaria Control Programme due to increased parasite resistance to chloroquine.<ref name=Eastman2009>{{cite journal|title=Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria |author2-link=David A. Fidock|vauthors=Eastman RT, Fidock DA |journal=Nature Reviews Microbiology |volume=7 |pages=864–874 |date=2009 |issue=12 |doi=10.1038/nrmicro2239|pmc=2901398 |pmid=19881520}}</ref> By the late 1980s, the use of piperaquine as an antimalarial monotherapy diminished as increasing parasite resistance to piperaquine was observed.<ref name=Davis/> Beginning in the 1990s, piperaquine was tested and adopted as a partner drug for ].<ref name=Davis/> |
|
|
|
|
|
== References == |
|
|
{{Reflist|colwidth=30em}} |
|
|
{{Antimalarials|state=collapsed}} |
|
|
|
|
|
] |
|
] |
|
] |
|
] |
|
] |
|
] |
|
] |
|
] |
|
|
] |
|
|
|
|
|
|
|
|
{{antiinfective-drug-stub}} |