PRIMAQUINE PHOSPHATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C15H21N3O.2H3O4P
Molecular Weight	455.3371
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OP(O)(O)=O.OP(O)(O)=O.COC1=CC(NC(C)CCCN)=C2N=CC=CC2=C1

InChI

InChIKey=GJOHLWZHWQUKAU-UHFFFAOYSA-N

InChI=1S/C15H21N3O.2H3O4P/c1-11(5-3-7-16)18-14-10-13(19-2)9-12-6-4-8-17-15(12)14;2*1-5(2,3)4/h4,6,8-11,18H,3,5,7,16H2,1-2H3;2*(H3,1,2,3,4)

HIDE SMILES / InChI

Molecular Formula	H3O4P
Molecular Weight	97.9952
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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
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
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
Primaquine induced hemolysis in a Thai soldier.	1989 Dec	2639511
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
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
Inhibitors of human immunodeficiency virus integrase.	1993 Mar 15	8460151
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
Dapsone- and primaquine-induced methemoglobinemia in HIV-infected individuals.	1996 Aug 15	8757424
Efficacy of 101 antimicrobials and other agents on the development of Cryptosporidium parvum in vitro.	1996 Dec	9039272
Drug-induced methaemoglobinaemia. Treatment issues.	1996 Jun	8828017
[Hemolysis and primaquine treatment. Preliminary report].	1997	9685977
Prediction of aryl hydrocarbon receptor-mediated enzyme induction of drugs and chemicals by mRNA quantification.	1998 Dec	9860486
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
Formulation and evaluation of taste masked oral reconstitutable suspension of primaquine phosphate.	2008	18770047
Imported malaria in a cosmopolitan European city: a mirror image of the world epidemiological situation.	2008 Apr 8	18397524
Identification of differentially expressed genes after acute exposure to bulaquine (CDRI 80/53) in mice liver.	2008 Dec	18684221
[In vitro dissolution profile of primaquine tablets available for malaria treatment in Brazil].	2008 Jan-Feb	18368269
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
Formulation and evaluation of primaquine phosphate taste-masked rapidly disintegrating tablet.	2008 Oct	18812020
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
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
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
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
Flavones as isosteres of 4(1H)-quinolones: discovery of ligand efficient and dual stage antimalarial lead compounds.	2013 Nov	24125849
N-cinnamoylation of antimalarial classics: quinacrine analogues with decreased toxicity and dual-stage activity.	2014 Feb	24474655
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 15:06:04 GMT 2023` Edited by `admin` on `Fri Dec 15 15:06:04 GMT 2023`
Record UNII	H0982HF78B
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PRIMAQUINE PHOSPHATE

Common Name

English

1,4-PENTANEDIAMINE, N4-(6-METHOXY-8-QUINOLINYL)-, PHOSPHATE (1:2)

Systematic Name

English

MALQUINE

Brand Name

English

PRIMAQUINE PHOSPHATE [USP-RS]

Common Name

English

PRIMAQUINE DIPHOSPHATE [EP MONOGRAPH]

Common Name

English

PRIMAQUINE PHOSPHATE [MART.]

Common Name

English

PRIMAQUINE DIPHOSPHATE [WHO-IP]

Common Name

English

PRIMAQUINI DIPHOSPHAS [WHO-IP LATIN]

Common Name

English

Primaquine phosphate [WHO-DD]

Common Name

English

PRIMAQUINE PHOSPHATE [JAN]

Common Name

English

CAMDEN

Brand Name

English

PRIMAQUINE PHOSPHATE [ORANGE BOOK]

Common Name

English

8-(4-AMINO-1-METHYLBUTYLAMINO)-6-METHOXYQUINOLINE DIPHOSPHATE

Systematic Name

English

PRIMAQUINE PHOSPHATE [VANDF]

Common Name

English

NSC-149765

Code

English

PRIMAQUINE PHOSPHATE [USP MONOGRAPH]

Common Name

English

PRIMAQUINE DIPHOSPHATE [MI]

Common Name

English

WR 2975

Code

English

PRIMAQUINE DIPHOSPHATE

Common Name

English

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

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

74793