PRIMAQUINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C15H21N3O
Molecular Weight	259.3467
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC(NC(C)CCCN)=C2N=CC=CC2=C1

InChI

InChIKey=INDBQLZJXZLFIT-UHFFFAOYSA-N

InChI=1S/C15H21N3O/c1-11(5-3-7-16)18-14-10-13(19-2)9-12-6-4-8-17-15(12)14/h4,6,8-11,18H,3,5,7,16H2,1-2H3

HIDE SMILES / InChI

Molecular Formula	C15H21N3O
Molecular Weight	259.3467
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.cdri.res.in/Bulaquin.aspx | http://www.insa.nic.in/writereaddata/UpLoadedFiles/PINSA/Vol69B_2003_6_Art02.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2008/008316s017lbl.pdf

Primaquine is a oral medication used to treat and prevent malaria and to treat Pneumocystis pneumonia. Specifically it is used for malaria due to Plasmodium vivax and Plasmodium ovale along with other medications and for prevention if other options cannot be used. Primaquine is an alternative treatment for Pneumocystis pneumonia together with clindamycin. Primaquine is lethal to P. vivax and P. ovale in the liver stage, and also to P. vivax in the blood stage through its ability to do oxidative damage to the cell. However, the exact mechanism of action is not fully understood. Primaquine is well-absorbed in the gut and extensively distributed in the body without accumulating in red blood cells. Administration of primaquine with food or grapefruit juice increases its oral bioavailibity. In blood, about 20% of circulating primaquine is protein-bound, with preferential binding to the acute phase protein orosomucoid. With a half-life on the order of 6 hours, it is quickly metabolized by liver enzymes to carboxyprimaquine, which does not have anti-malarial activity. Common side effects of primaquine administration include nausea, vomiting, and stomach cramps. Primaquine phosphate is recommended only for the radical cure of vivax malaria, the prevention of relapse in vivax malaria, or following the termination of chloroquine phosphate suppressive therapy in an area where vivax malaria is endemic. Patients suffering from an attack of vivax malaria or having parasitized red blood cells should receive a course of chloroquine phosphate, which quickly destroys the erythrocytic parasites and terminates the paroxysm. Primaquine phosphate should be administered concurrently in order to eradicate the exoerythrocytic parasites in a dosage of 1 tablet (equivalent to 15 mg base) daily for 14 days.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Quinone reductase 2 12 Target ID: CHEMBL3959 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21074425	Inhibitor 8297		7.5 µM [IC50]
Chloroquine resistance transporter 3 Target ID: CHEMBL1795182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900883	Inhibitor 8297		68.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Plasmodium vivax malaria 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16969059	Curative		Approved 8429	AABLAQUIN Approved Use Treatment and prevention of p. vivax. Launch Date 2000
Plasmodium vivax malaria 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/008316s017lbl.pdf	Curative		Approved 8429	PRIMAQUINE Approved Use Primaquine phosphate is indicated for the radical cure (prevention of relapse) of vivax malaria. Launch Date 1952

C_max

Value	Dose	Analyte	Population
53 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027117/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
104 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027117/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
66 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027118/	15 mg 1 times / day multiple, oral dose: 15 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
65 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027118/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
0.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027117/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027117/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
443 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027118/	15 mg 1 times / day multiple, oral dose: 15 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
468 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027118/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
5.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027117/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027117/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027118/	15 mg 1 times / day multiple, oral dose: 15 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4027118/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PRIMAQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
30 mg 1 times / day steady, oral Highest studied dose Dose: 30 mg, 1 times / day Route: oral Route: steady Dose: 30 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/	unhealthy, adult n = 120 Health Status: unhealthy Condition: Plasmodium vivax parasite Age Group: adult Sex: M Population Size: 120 Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/	Other AEs: Malaise, Headache... Other AEs: Malaise (1 patient) Headache (2 patients) Nausea (1 patient) Pyrexia (1 patient) Vomiting (1 patient) Dizziness (1 patient) Asthenia (1 patient) Pruritus (1 patient) Haemoglobin decreased (1 patient) Dyspepsia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/
0.6 mg/kg 1 times / day multiple, oral Highest studied dose Dose: 0.6 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.6 mg/kg, 1 times / day Co-administed with:: (artesunate) 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/12932090/	unhealthy, adult n = 18 Health Status: unhealthy Condition: acute, symptomatic Plasmodium vivax malaria Age Group: adult Sex: unknown Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/12932090/	Disc. AE: Hematocrit decreased... AEs leading to discontinuation/dose reduction: Hematocrit decreased (4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/12932090/
15 mg 1 times / day steady, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/	unhealthy, adult n = 118 Health Status: unhealthy Condition: Plasmodium vivax parasite Age Group: adult Sex: M Population Size: 118 Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/	Other AEs: Malaise, Headache... Other AEs: Malaise (4 patients) Headache (2 patients) Nausea (1 patient) Decreased appetite (3 patients) Pyrexia (1 patient) Vomiting (1 patient) Dizziness (1 patient) Asthenia (1 patient) Arthralgia (1 patient) Muscle spasms (1 patient) Dyspnoea exertional (1 patient) Diarrhoea (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/
15 mg 1 times / day steady, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/	unhealthy, adult n = 120 Health Status: unhealthy Condition: Plasmodium vivax parasite Age Group: adult Sex: M Population Size: 120 Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/	Other AEs: Malaise, Headache... Other AEs: Malaise (3 patients) Headache (1 patient) Nausea (2 patients) Pyrexia (1 patient) Vomiting (1 patient) Myalgia (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/26366319/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP3A4/5 278 P-gp 1461 OATP1A2 35 OATP1B1 788	CYP2C19 991 CYP1A2 1054	CYP1A2 701

Drug as perpetrator

Target	Modality	Activity
CYP3A4/5 335	inhibitor 3277 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=32 Page: (PMDA_I100_1 in Japanese) 32	yes [IC50 19.4 uM]
OATP1A2 35	inhibitor 3277 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_22800AMX00403000_A100_1.pdf#page=16 Page: (PMDA_A100_1 in Japanese) 16	yes [IC50 5.6 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=32 Page: (PMDA_I100_1 in Japanese) 32, 36	yes [Ki 0.22 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=32 Page: (PMDA_I100_1 in Japanese) 32	yes [Ki 23 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=32 Page: (PMDA_I100_1 in Japanese) 32, 36	yes
OATP1B1 803	inhibitor 3277 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_22800AMX00403000_A100_1.pdf#page=16 Page: (PMDA_A100_1 in Japanese) 16	yes
P-gp 1650	inhibitor 3277 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=32 Page: (PMDA_I100_1 in Japanese) 32	yes

Drug as victim

Target	Modality	Activity
CYP3A4 1737	substrate 3367 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=30 Page: (PMDA_I100_1 in Japanese) 29-30	minor [Km 37000 uM]
CYP2C19 991	substrate 3367 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=30 Page: (PMDA_I100_1 in Japanese) 29-30	minor [Km 52000 uM]
CYP2C9 1037	substrate 3367 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=30 Page: (PMDA_I100_1 in Japanese) 29-30	no
CYP2D6 1217	substrate 3367 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=30 Page: (PMDA_I100_1 in Japanese) 29-30	weak [Km 37000 uM]
CYP1A2 1054	substrate 3367 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_2800AMX00403000_I100_1.pdf#page=30 Page: (PMDA_I100_1 in Japanese) 29-30	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.pmda.go.jp/drugs/2016/P20160309001/780069000_22800AMX00403000_A100_1.pdf#page=10, https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/008316s023lbl.pdf#page=3 Page: (PMDA_A100_1 in Japanese) 10, (FDA label) 3

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8405	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8405
ChemicalBook	CB0875785	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0875785
MolPort	MolPort-001-794-628	https://www.molport.com/shop/molecule-link/MolPort-001-794-628
eMolecules	1077024	https://www.emolecules.com/cgi-bin/more?vid=1077024

PubMed

Title	Date	PubMed
Potentiation of the curative action of primaquine in vivax malaria by quinine and chloroquine.	1955 Aug	13242948
Methemoglobinemia provoked by malarial chemoprophylaxis in Vietnam.	1968 Nov 21	5686480
Simultaneous drug reactions in the same patient. Chloroquine-Primaquine sensitivity.	1970 Apr 27	5467364
Reaction to primaquine.	1980 Mar	7356244
The treatment of malaria in glucose-6-phosphate dehydrogenase deficient patients in Sabah.	1981 Dec	7325735
Primaquine-chloroquine prophylaxis against malaria in Southeast-Asian refugees entering South Australia.	1984 Mar 17	6366489
Pharmacokinetics of primaquine in man. I. Studies of the absolute bioavailability and effects of dose size.	1985 Jun	4027117
[Hemolytic reaction due to administration of primaquine].	1986 Apr	3742573
Drug- and chemical-induced methaemoglobinaemia. Clinical features and management.	1986 Jul-Aug	3537620
Activity of clindamycin with primaquine against Pneumocystis carinii in vitro and in vivo.	1988 Jun	3261959
Immunogenicity of amodiaquine in the rat.	1990	2210868
Causal prophylactic activity of a new 8-aminoquinoline derivative against Plasmodium cynomolgi B in rhesus monkeys.	1990 May	2397941
Effect of anti-relapse antimalarial compound CDRI 80/53 and primaquine on hepatic mixed function oxidase system of rhesus monkey.	1990 Nov-Dec	2075158
The effect of primaquine on the ultrastructural morphology of Pneumocystis carinii.	1991 Nov-Dec	1818151
Isolation and characterization of rat lung Pneumocystis carinii gp120.	1991 Nov-Dec	1818123
Acute intravascular haemolysis in Vanuatu following a single dose of primaquine in individuals with glucose-6-phosphate dehydrogenase deficiency.	1992 Oct	1404560
Inhibitors of human immunodeficiency virus integrase.	1993 Mar 15	8460151
New drug developments for opportunistic infections in immunosuppressed patients: Pneumocystis carinii.	1995 Nov 24	7490723
Dapsone- and primaquine-induced methemoglobinemia in HIV-infected individuals.	1996 Aug 15	8757424
In vitro cultivation of Chinese strains of Babesia spp.	2002 May	12051608
Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells.	2002 Nov	12451431
Time-dependent transcriptional induction of CYP1A1, CYP1A2 and CYP1B1 mRNAs by H+/K+ -ATPase inhibitors and other xenobiotics.	2003 Feb	12623754
Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data.	2003 Sep	12920490
Piperaquine: a resurgent antimalarial drug.	2005	15610051
Glucose-6-phosphate dehydrogenase deficiency in two returning Operation Iraqi Freedom soldiers who developed hemolytic anemia while receiving primaquine prophylaxis for malaria.	2005 Apr	15916292
Primaquine-induced hemolytic anemia: role of membrane lipid peroxidation and cytoskeletal protein alterations in the hemotoxicity of 5-hydroxyprimaquine.	2005 Aug	15840764
Exotic diseases of dogs and cats at risk of importation to Ireland.	2005 May 1	21851670
Glycodendrimeric nanoparticulate carriers of primaquine phosphate for liver targeting.	2005 May 13	15848007
Evaluation of anti-malarial effects of mass chemoprophylaxis in the Republic of Korea army.	2005 Oct	16224140
[Haemolysis due to primaquine in 3 cases].	2006 Feb 28	16866141
Pharmacokinetics of piperaquine after repeated oral administration of the antimalarial combination CV8 in 12 healthy male subjects.	2006 May	16570188
Drug, dosage, activity, studies of antimalarials by physical methods--II.	2007 May 20	18084644
Congenital malaria in the United States: a review of cases from 1966 to 2005.	2007 Nov	17984408
HepaRG cells as an in vitro model for evaluation of cytochrome P450 induction in humans.	2008 Jan	17954527
Development and validation of UPLC method for determination of primaquine phosphate and its impurities.	2008 Jan 22	18029132
[In vitro dissolution profile of primaquine tablets available for malaria treatment in Brazil].	2008 Jan-Feb	18368269
Novel triazine JPC-2067-B inhibits Toxoplasma gondii in vitro and in vivo.	2008 Mar 5	18320016
Monkey malaria in a European traveler returning from Malaysia.	2008 Sep	18760013
Cytochrome P(450)-dependent toxic effects of primaquine on human erythrocytes.	2009 Nov 15	19616568
Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.	2010 Dec	20829430
Feline babesiosis.	2010 Feb	20230438
The Summary Index of Malaria Surveillance (SIMS): a stable index of malaria within India.	2010 Feb 11	20181218
An open-label, randomised study of dihydroartemisinin-piperaquine versus artesunate-mefloquine for falciparum malaria in Asia.	2010 Jul 30	20689583
In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals.	2010 May	20194698
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003
Novel potent metallocenes against liver stage malaria.	2012 Mar	22155838
Understanding the mechanisms for metabolism-linked hemolytic toxicity of primaquine against glucose 6-phosphate dehydrogenase deficient human erythrocytes: evaluation of eryptotic pathway.	2012 Mar 29	22330256
Characterization of Plasmodium liver stage inhibition by halofuginone.	2012 May	22438279
N-cinnamoylated chloroquine analogues as dual-stage antimalarial leads.	2013 Jan 24	23273038
Quinolin-4(1H)-imines are potent antiplasmodial drugs targeting the liver stage of malaria.	2013 Jun 13	23701465

Patents

Sample Use Guides

In Vivo Use Guide

Patients recieved 25 mg once daily for 7 days.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:46:25 GMT 2023` Edited by `admin` on `Fri Dec 15 15:46:25 GMT 2023`
Record UNII	MVR3634GX1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PRIMAQUINE

Official Name

English

PRIMAQUINE [VANDF]

Common Name

English

PRIMAQUINE [MI]

Common Name

English

SN-13272

Code

English

(±)-PRIMAQUINE

Common Name

English

Primaquine [WHO-DD]

Common Name

English

KANAPRIM

Brand Name

English

WR-2975

Code

English

PRIMACHIN

Common Name

English

NEO-QUIPENYL

Brand Name

English

MALIRIDE

Brand Name

English

NSC-27296

Code

English

primaquine [INN]

Common Name

English

QUINOLINE, 8-((4-AMINO-1-METHYLBUTYL)AMINO)-6-METHOXY-

Systematic Name

English

1,4-PENTANEDIAMINE, N4-(6-METHOXY-8-QUINOLINYL)-

Systematic Name

English

Classification Tree Code System Code

LIVERTOX

NBK548031