Identification

Name
Piperaquine
Accession Number
DB13941
Type
Small Molecule
Groups
Approved, Investigational
Description

Piperaquine is an antimalarial agent first synthesized in the 1960's and used throughout China [1]. Its use declined in the 1980's as piperaquine resistant strains of Plasmodium falciparum appeared and artemisinin derivatives became available. It has come back into use in combination with the artemisinin derivative Artenimol as part of the combination product Eurartesim [Label]. Eurartesim was first authorized for market by the European Medicines Agency in October 2011.

Structure
Thumb
Synonyms
  • 1,3-bis[4-(7-chloroquinolin-4-yl)piperazin-1-yl]propane
Product Ingredients
IngredientUNIICASInChI Key
Piperaquine tetraphosphateIHB5WLO51Q911061-10-4OAKKJVUSSVZQRF-UHFFFAOYSA-N
Categories
UNII
A0HV2Q956Y
CAS number
4085-31-8
Weight
Average: 535.52
Monoisotopic: 534.2065505
Chemical Formula
C29H32Cl2N6
InChI Key
UCRHFBCYFMIWHC-UHFFFAOYSA-N
InChI
InChI=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
IUPAC Name
7-chloro-4-(4-{3-[4-(7-chloroquinolin-4-yl)piperazin-1-yl]propyl}piperazin-1-yl)quinoline
SMILES
ClC1=CC2=C(C=C1)C(=CC=N2)N1CCN(CCCN2CCN(CC2)C2=CC=NC3=C2C=CC(Cl)=C3)CC1

Pharmacology

Indication

For the treatment of uncomplicated Plasmodium falciparum infection in adults, children, and infants aged 6 months and up weighing over 5 kg [Label]. Used in combination with Artenimol.

Pharmacodynamics

Piperaquine inhibits the P. Falciparum parasite's haem detoxification pathway [4].

Mechanism of action

The mechanism of piperaquine inhibition of the haem detoxification pathway is unknown but is expected to be similar to that of Chloroquine.

Absorption

Piperaquine is slowly absorbed and exhibits multiple peaks in its plasma concentration curve suggestive of enterohepatic recycling occurring alongside the absorption process [4]. Due to this complication there is no discreet value for bioavailability but piperaquine is highly absorbed into systemic circulation. When taken with food, Cmax increases by 217% and mean exposure increases by 177%. Tmax is not affected by food and remains around 5 h [Label]. Piperaquine has been observed to accumulate more in females to a degree of 30-50% more than males [Label]. It also collects in red blood cells similar to Artenimol.

Volume of distribution

Piperaquine is thought to distribute into a central compartment with an apparent volume of 26.7 L/kg, and two peripheral compartments with apparent volumes of 76.8 L/kg and 617 L/kg [4]. These combine for a total volume of distribution of 720.5 L/kg.

Protein binding

Piperaquine's binding to plasma proteins is considered to be virtually complete [4]. It has been measured to be >99% in humans, rats, and dogs.

Metabolism

Piperaquine undergoes N-dealkylation, separating its aliphatic bridge from one of the nitrogen-containing rings [3]. The resulting aldehyde is then oxidized to a carboxylic acid to form metabolite 1 (M1). The same nitrogen-containing rings can also undergo hydroxylation at one of two sites to form M3 or M4. M2 is formed via N-oxidation of one of the nitrogens in the quinoline groups at either side of the molecule. M5 results when both of these nitrogens are oxidized. M1 and M2 are the major metabolism products [Label]. Each of these metabolites were observed in the urine.

Route of elimination

Piperaquine is mainly excreted in the feces with a negligible amount in the urine [Label].

Half life

The terminal elimination half-life was observed to be 576h or 24 days [4]. This is thought to be due to the extensive distribution of piperaquine.

Clearance

The mean apparent total clearance has been observed to be 1.12 L/h/kg in adult malaria patients [4].

Toxicity

Studies of piperaquine in monkeys and dogs have shown some hepatotoxicity and reversible depression in white blood cells and neutrophils [Label]. Additional observations include infiltration of macrophages with intracytoplasmic basophilic granular material consistent with phospholipidosis and degenerative lesions in numerous organs and tissues. These effects were seen at exposure levels similar to clinical dosing in humans. At high doses, piperaquine can interfere with cardiac conduction and produce effects on blood pressure. Mild phototoxicity has been observed with piperaquine in rats exposed to UV light.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe metabolism of Piperaquine can be decreased when combined with Abiraterone.Approved
AcepromazineThe serum concentration of Acepromazine can be increased when it is combined with Piperaquine.Approved, Vet Approved
AceprometazineThe serum concentration of Aceprometazine can be increased when it is combined with Piperaquine.Approved
Acetyl sulfisoxazoleThe metabolism of Piperaquine can be decreased when combined with Acetyl sulfisoxazole.Approved, Vet Approved
AlimemazineThe serum concentration of Alimemazine can be increased when it is combined with Piperaquine.Approved, Vet Approved
AmiodaroneThe metabolism of Piperaquine can be decreased when combined with Amiodarone.Approved, Investigational
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Piperaquine.Approved, Investigational
ApalutamideThe serum concentration of Piperaquine can be decreased when it is combined with Apalutamide.Approved, Investigational
AprepitantThe serum concentration of Piperaquine can be increased when it is combined with Aprepitant.Approved, Investigational
ArmodafinilThe metabolism of Piperaquine can be decreased when combined with Armodafinil.Approved, Investigational
ArtemetherThe risk or severity of QTc prolongation can be increased when Piperaquine is combined with Artemether.Approved
AsunaprevirThe serum concentration of Asunaprevir can be increased when it is combined with Piperaquine.Approved, Investigational, Withdrawn
AtazanavirThe metabolism of Piperaquine can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Piperaquine can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe risk or severity of adverse effects can be increased when Piperaquine is combined with Atorvastatin.Approved
BL-1020The serum concentration of BL-1020 can be increased when it is combined with Piperaquine.Investigational
BoceprevirThe metabolism of Piperaquine can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Piperaquine can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Piperaquine can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Piperaquine.Approved
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Piperaquine.Approved, Investigational
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Piperaquine.Approved
CapecitabineThe metabolism of Piperaquine can be decreased when combined with Capecitabine.Approved, Investigational
CarbamazepineThe metabolism of Piperaquine can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Piperaquine can be increased when it is combined with Ceritinib.Approved
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Piperaquine.Approved, Withdrawn
ChloramphenicolThe metabolism of Piperaquine can be decreased when combined with Chloramphenicol.Approved, Vet Approved
ChlorproethazineThe serum concentration of Chlorproethazine can be increased when it is combined with Piperaquine.Experimental
ChlorpromazineThe serum concentration of Chlorpromazine can be increased when it is combined with Piperaquine.Approved, Investigational, Vet Approved
CholecalciferolThe metabolism of Piperaquine can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Piperaquine.Approved, Investigational
CimetidineThe metabolism of Piperaquine can be decreased when combined with Cimetidine.Approved, Investigational
CitalopramThe metabolism of Piperaquine can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Piperaquine can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Piperaquine can be decreased when combined with Clemastine.Approved, Investigational
ClotrimazoleThe metabolism of Piperaquine can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Piperaquine can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Piperaquine.Approved, Investigational
CrisaboroleThe metabolism of Piperaquine can be decreased when combined with Crisaborole.Approved, Investigational
CrizotinibThe metabolism of Piperaquine can be decreased when combined with Crizotinib.Approved
CurcuminThe metabolism of Piperaquine can be decreased when combined with Curcumin.Approved, Investigational
CyclosporineThe metabolism of Piperaquine can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Piperaquine can be decreased when it is combined with Dabrafenib.Approved, Investigational
DapsoneThe risk or severity of adverse effects can be increased when Piperaquine is combined with Dapsone.Approved, Investigational
DarunavirThe metabolism of Piperaquine can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Piperaquine can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Piperaquine can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Piperaquine can be decreased when combined with Delavirdine.Approved
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Piperaquine.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Piperaquine.Approved, Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Piperaquine.Experimental
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Piperaquine.Approved, Investigational
DiltiazemThe metabolism of Piperaquine can be decreased when combined with Diltiazem.Approved, Investigational
DosulepinThe metabolism of Piperaquine can be decreased when combined with Dosulepin.Approved
DoxycyclineThe metabolism of Piperaquine can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Piperaquine can be decreased when combined with Dronedarone.Approved
EfavirenzThe metabolism of Piperaquine can be decreased when combined with Efavirenz.Approved, Investigational
EnzalutamideThe serum concentration of Piperaquine can be decreased when it is combined with Enzalutamide.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Piperaquine.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Piperaquine.Approved
ErythromycinThe metabolism of Piperaquine can be decreased when combined with Erythromycin.Approved, Investigational, Vet Approved
Eslicarbazepine acetateThe metabolism of Piperaquine can be decreased when combined with Eslicarbazepine acetate.Approved
EsomeprazoleThe metabolism of Piperaquine can be decreased when combined with Esomeprazole.Approved, Investigational
EtravirineThe metabolism of Piperaquine can be decreased when combined with Etravirine.Approved
FloxuridineThe metabolism of Piperaquine can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Piperaquine can be decreased when combined with Fluconazole.Approved, Investigational
FluorouracilThe metabolism of Piperaquine can be decreased when combined with Fluorouracil.Approved
FluoxetineThe metabolism of Piperaquine can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluphenazineThe serum concentration of Fluphenazine can be increased when it is combined with Piperaquine.Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Piperaquine.Approved
FluvoxamineThe metabolism of Piperaquine can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Piperaquine can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Piperaquine can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Piperaquine can be increased when combined with Fosphenytoin.Approved, Investigational
Fusidic AcidThe serum concentration of Piperaquine can be increased when it is combined with Fusidic Acid.Approved, Investigational
GemfibrozilThe metabolism of Piperaquine can be decreased when combined with Gemfibrozil.Approved
IbrutinibThe serum concentration of Ibrutinib can be increased when it is combined with Piperaquine.Approved
IdelalisibThe metabolism of Piperaquine can be decreased when combined with Idelalisib.Approved
ImatinibThe metabolism of Piperaquine can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Piperaquine can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Piperaquine can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoleThe serum concentration of Piperaquine can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe metabolism of Piperaquine can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Piperaquine can be decreased when combined with Isoniazid.Approved, Investigational
IsradipineThe metabolism of Piperaquine can be decreased when combined with Isradipine.Approved, Investigational
ItraconazoleThe metabolism of Piperaquine can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Piperaquine can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Piperaquine can be decreased when combined with Ketoconazole.Approved, Investigational
LeflunomideThe metabolism of Piperaquine can be decreased when combined with Leflunomide.Approved, Investigational
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Piperaquine.Approved, Investigational
LobeglitazoneThe metabolism of Piperaquine can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe metabolism of Piperaquine can be decreased when combined with Lopinavir.Approved
LorpiprazoleThe serum concentration of Piperaquine can be increased when it is combined with Lorpiprazole.Approved
LosartanThe metabolism of Piperaquine can be decreased when combined with Losartan.Approved
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Piperaquine.Approved, Investigational
LuliconazoleThe serum concentration of Piperaquine can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Piperaquine can be decreased when it is combined with Lumacaftor.Approved
LumefantrineThe risk or severity of QTc prolongation can be increased when Piperaquine is combined with Lumefantrine.Approved
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Piperaquine.Illicit, Investigational, Withdrawn
ManidipineThe metabolism of Piperaquine can be decreased when combined with Manidipine.Approved, Investigational
MesoridazineThe serum concentration of Mesoridazine can be increased when it is combined with Piperaquine.Approved, Investigational
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Piperaquine.Experimental
MethotrimeprazineThe serum concentration of Methotrimeprazine can be increased when it is combined with Piperaquine.Approved, Investigational
Methylene blueThe serum concentration of Methylene blue can be increased when it is combined with Piperaquine.Approved, Investigational
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Piperaquine.Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Piperaquine.Approved
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Piperaquine.Experimental
MidostaurinThe metabolism of Piperaquine can be decreased when combined with Midostaurin.Approved, Investigational
MifepristoneThe serum concentration of Piperaquine can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Piperaquine can be decreased when it is combined with Mitotane.Approved
MoclobemideThe metabolism of Piperaquine can be decreased when combined with Moclobemide.Approved, Investigational
ModafinilThe metabolism of Piperaquine can be decreased when combined with Modafinil.Approved, Investigational
MoricizineThe serum concentration of Moricizine can be increased when it is combined with Piperaquine.Approved, Investigational, Withdrawn
NabiloneThe metabolism of Piperaquine can be decreased when combined with Nabilone.Approved, Investigational
NefazodoneThe metabolism of Piperaquine can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Piperaquine can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Piperaquine can be increased when it is combined with Netupitant.Approved, Investigational
NevirapineThe metabolism of Piperaquine can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Piperaquine can be decreased when combined with Nicardipine.Approved, Investigational
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Piperaquine.Approved, Investigational
NilotinibThe metabolism of Piperaquine can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Piperaquine can be decreased when combined with Olaparib.Approved
OmeprazoleThe metabolism of Piperaquine can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Piperaquine can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Piperaquine can be increased when it is combined with Palbociclib.Approved, Investigational
PantoprazoleThe metabolism of Piperaquine can be decreased when combined with Pantoprazole.Approved
PentobarbitalThe metabolism of Piperaquine can be increased when combined with Pentobarbital.Approved, Investigational, Vet Approved
PerazineThe serum concentration of Perazine can be increased when it is combined with Piperaquine.Approved, Investigational
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Piperaquine.Approved, Investigational, Vet Approved, Withdrawn
PerphenazineThe serum concentration of Perphenazine can be increased when it is combined with Piperaquine.Approved
PhenobarbitalThe metabolism of Piperaquine can be increased when combined with Phenobarbital.Approved, Investigational
PhenytoinThe metabolism of Piperaquine can be increased when combined with Phenytoin.Approved, Vet Approved
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Piperaquine.Approved
PitolisantThe serum concentration of Piperaquine can be decreased when it is combined with Pitolisant.Approved, Investigational
PosaconazoleThe metabolism of Piperaquine can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Piperaquine.Approved
PrimidoneThe metabolism of Piperaquine can be increased when combined with Primidone.Approved, Vet Approved
ProchlorperazineThe serum concentration of Prochlorperazine can be increased when it is combined with Piperaquine.Approved, Vet Approved
PromazineThe serum concentration of Promazine can be increased when it is combined with Piperaquine.Approved, Vet Approved
PromethazineThe serum concentration of Promethazine can be increased when it is combined with Piperaquine.Approved, Investigational
PropericiazineThe serum concentration of Propericiazine can be increased when it is combined with Piperaquine.Approved, Investigational
PropiopromazineThe serum concentration of Propiopromazine can be increased when it is combined with Piperaquine.Vet Approved
PyrimethamineThe metabolism of Piperaquine can be decreased when combined with Pyrimethamine.Approved, Investigational, Vet Approved
QuinineThe metabolism of Piperaquine can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Piperaquine can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Piperaquine can be increased when combined with Rifabutin.Approved, Investigational
RifampicinThe metabolism of Piperaquine can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Piperaquine can be increased when combined with Rifapentine.Approved, Investigational
RilpivirineThe serum concentration of Rilpivirine can be increased when it is combined with Piperaquine.Approved
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Piperaquine.Approved
RucaparibThe metabolism of Piperaquine can be decreased when combined with Rucaparib.Approved, Investigational
SaquinavirThe metabolism of Piperaquine can be decreased when combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Piperaquine can be decreased when used in combination with Sarilumab.Approved, Investigational
SecobarbitalThe metabolism of Piperaquine can be increased when combined with Secobarbital.Approved, Vet Approved
SertralineThe metabolism of Piperaquine can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Piperaquine can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Piperaquine can be decreased when it is combined with Siltuximab.Approved, Investigational
SimeprevirThe serum concentration of Piperaquine can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Piperaquine.Approved
SorafenibThe metabolism of Piperaquine can be decreased when combined with Sorafenib.Approved, Investigational
St. John's WortThe serum concentration of Piperaquine can be decreased when it is combined with St. John's Wort.Approved, Investigational, Nutraceutical
StiripentolThe serum concentration of Piperaquine can be increased when it is combined with Stiripentol.Approved
SulfadiazineThe metabolism of Piperaquine can be decreased when combined with Sulfadiazine.Approved, Investigational, Vet Approved
SulfamethoxazoleThe metabolism of Piperaquine can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Piperaquine can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Piperaquine can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Piperaquine can be decreased when combined with Telithromycin.Approved
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Piperaquine.Experimental
ThiazinamThe serum concentration of Thiazinam can be increased when it is combined with Piperaquine.Experimental
ThiethylperazineThe serum concentration of Thiethylperazine can be increased when it is combined with Piperaquine.Withdrawn
ThioproperazineThe serum concentration of Thioproperazine can be increased when it is combined with Piperaquine.Approved
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Piperaquine.Approved, Withdrawn
TicagrelorThe metabolism of Piperaquine can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Piperaquine can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Piperaquine can be decreased when it is combined with Tocilizumab.Approved
TolbutamideThe metabolism of Piperaquine can be decreased when combined with Tolbutamide.Approved, Investigational
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Piperaquine.Approved
TopiramateThe metabolism of Piperaquine can be decreased when combined with Topiramate.Approved
TopiroxostatThe metabolism of Piperaquine can be decreased when combined with Topiroxostat.Approved, Investigational
TranylcypromineThe metabolism of Piperaquine can be decreased when combined with Tranylcypromine.Approved, Investigational
TrifluoperazineThe serum concentration of Trifluoperazine can be increased when it is combined with Piperaquine.Approved, Investigational
TriflupromazineThe serum concentration of Triflupromazine can be increased when it is combined with Piperaquine.Approved, Vet Approved
TrimethoprimThe metabolism of Piperaquine can be decreased when combined with Trimethoprim.Approved, Vet Approved
Valproic AcidThe metabolism of Piperaquine can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Piperaquine can be decreased when combined with Valsartan.Approved, Investigational
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Piperaquine.Approved
VenlafaxineThe metabolism of Piperaquine can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Piperaquine can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Piperaquine can be decreased when combined with Voriconazole.Approved, Investigational
ZafirlukastThe metabolism of Piperaquine can be decreased when combined with Zafirlukast.Approved, Investigational
ZiprasidoneThe metabolism of Piperaquine can be decreased when combined with Ziprasidone.Approved
ZucapsaicinThe metabolism of Piperaquine can be decreased when combined with Zucapsaicin.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Davis TM, Hung TY, Sim IK, Karunajeewa HA, Ilett KF: Piperaquine: a resurgent antimalarial drug. Drugs. 2005;65(1):75-87. [PubMed:15610051]
  2. Hoglund RM, Workman L, Edstein MD, Thanh NX, Quang NN, Zongo I, Ouedraogo JB, Borrmann S, Mwai L, Nsanzabana C, Price RN, Dahal P, Sambol NC, Parikh S, Nosten F, Ashley EA, Phyo AP, Lwin KM, McGready R, Day NP, Guerin PJ, White NJ, Barnes KI, Tarning J: Population Pharmacokinetic Properties of Piperaquine in Falciparum Malaria: An Individual Participant Data Meta-Analysis. PLoS Med. 2017 Jan 10;14(1):e1002212. doi: 10.1371/journal.pmed.1002212. eCollection 2017 Jan. [PubMed:28072872]
  3. Tarning J, Bergqvist Y, Day NP, Bergquist J, Arvidsson B, White NJ, Ashton M, Lindegardh N: Characterization of human urinary metabolites of the antimalarial piperaquine. Drug Metab Dispos. 2006 Dec;34(12):2011-9. doi: 10.1124/dmd.106.011494. Epub 2006 Sep 6. [PubMed:16956956]
  4. EMA: Eurartesim Assessment Report [Link]
External Links
ChemSpider
109031
ChEBI
91231
ChEMBL
CHEMBL303933
PharmGKB
PA166104279
Wikipedia
Piperaquine
ATC Codes
P01BF05 — Artenimol and piperaquine
FDA label
Download (904 KB)
MSDS
Download (107 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1, 2CompletedOtherPlasmodium Infections1
3CompletedPreventionHealthy Volunteers1
Not AvailableNot Yet RecruitingOtherControlled Human Malaria Infection / Gametocytes / Malaria caused by Plasmodium falciparum / Transmission1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0167 mg/mLALOGPS
logP5.53ALOGPS
logP5.27ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)8.47ChemAxon
Physiological Charge3ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area38.74 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity153.42 m3·mol-1ChemAxon
Polarizability59.56 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Drug is a moderately sensitive substrate for CYP3A4 (change in AUC >2 fold with enzyme inhibitor).
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. EMA: Eurartesim Assessment Report [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. EMA: Eurartesim Assessment Report [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. EMA: Eurartesim Assessment Report [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. EMA: Eurartesim Assessment Report [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. EMA: Eurartesim Assessment Report [Link]

Drug created on January 04, 2018 14:59 / Updated on July 02, 2018 21:01