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 9.4668482E11
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 -5.661792E11

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
The haemolytic effect of various regimens of primaquine with chloroquine in American Negroes with G6PD deficiency and the lack of an effect of various antimalarial suppressive agents on erythrocyte metabolism.	1967	4864652
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
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
Drug- and chemical-induced methaemoglobinaemia. Clinical features and management.	1986 Jul-Aug	3537620
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
Detection of antidrug IgG antibodies in patients with adverse drug reactions to amodiaquine.	1991	1959977
Effect of the antimalarial agents primaquine and (N'-3-acetyl-4-5-dihydro-2-furanyl)-N4-(6-methoxy-8-quinolinyl)1,4-pent ane-diamine on oxidative stress and antioxidant defences in mice.	1993 Nov 17	8250972
In vitro effects of artemisinin ether, cycloguanil hydrochloride (alone and in combination with sulfadiazine), quinine sulfate, mefloquine, primaquine phosphate, trifluoperazine hydrochloride, and verapamil on Toxoplasma gondii.	1994 Jun	8092843
[Primaquine and travelers from the Arab world. A report and recommendations].	1995	9813483
New drug developments for opportunistic infections in immunosuppressed patients: Pneumocystis carinii.	1995 Nov 24	7490723
Prediction of aryl hydrocarbon receptor-mediated enzyme induction of drugs and chemicals by mRNA quantification.	1998 Dec	9860486
Effect of primaquine standard dose (15 mg/day for 14 days) in the treatment of vivax malaria patients in Thailand.	2001 Dec	12041544
A meta-analysis of salvage therapy for Pneumocystis carinii pneumonia.	2001 Jun 25	11427101
Primaquine-induced hemolytic anemia: formation and hemotoxicity of the arylhydroxylamine metabolite 6-methoxy-8-hydroxylaminoquinoline.	2001 May	11303037
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
cAMP-dependent exocytosis and vesicle traffic regulate CFTR and fluid transport in rat jejunum in vivo.	2003 Feb	12529251
Conductometric and indirect AAS determination of antimalarials.	2003 Mar 26	12644205
Real-time investigation of the interaction between primaquine phosphate and bovine serum albumin (BSA) by piezoelectric quartz crystal impedance analysis.	2003 Oct 9	14511914
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
Feline babesiosis in South Africa: a review.	2004 Oct	15604490
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
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
Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I.	2006 Sep	16968913
In Vitro and In Vivo pharmacokinetic studies of bulaquine (analogue of primaquine), a novel antirelapse antimalarial, in rat, rabbit and monkey--highlighting species similarities and differences.	2007 Jul	17410524
Persistent binding of ligands to the aryl hydrocarbon receptor.	2007 Jul	17431010
Identification of differentially expressed genes after acute exposure to bulaquine (CDRI 80/53) in mice liver.	2008 Dec	18684221
Omeprazole transactivates human CYP1A1 and CYP1A2 expression through the common regulatory region containing multiple xenobiotic-responsive elements.	2008 Jul 1	18502397
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
Diverse chemicals including aryl hydrocarbon receptor ligands modulate transcriptional activity of the 3'immunoglobulin heavy chain regulatory region.	2009 Jun 30	19447539
Cytochrome P(450)-dependent toxic effects of primaquine on human erythrocytes.	2009 Nov 15	19616568
The Summary Index of Malaria Surveillance (SIMS): a stable index of malaria within India.	2010 Feb 11	20181218
Monitoring for Plasmodium falciparum drug resistance to artemisinin and artesunate in Binh Phuoc Province, Vietnam: 1998-2009.	2010 Jun 24	20573274
Blockade of hERG K(+) channel by antimalarial drug, primaquine.	2010 May	20512476
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
Primaquine or other 8-aminoquinoline for reducing Plasmodium falciparum transmission.	2015 Feb 19	25693791
Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects.	2015 Jan 5	25569083
Development of HepG2-derived cells expressing cytochrome P450s for assessing metabolism-associated drug-induced liver toxicity.	2016 Aug 5	26477383

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 UTC 2023` Edited by `admin` on `Fri Dec 15 15:46:25 UTC 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