PYRIMETHAMINE PAMOATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H16O6.C12H13ClN4
Molecular Weight	637.081
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1=C(C(N)=NC(N)=N1)C2=CC=C(Cl)C=C2.OC(=O)C3=C(O)C(CC4=C5C=CC=CC5=CC(C(O)=O)=C4O)=C6C=CC=CC6=C3

InChI

InChIKey=VJVWMYFEZGXNPC-UHFFFAOYSA-N

InChI=1S/C23H16O6.C12H13ClN4/c24-20-16(14-7-3-1-5-12(14)9-18(20)22(26)27)11-17-15-8-4-2-6-13(15)10-19(21(17)25)23(28)29;1-2-9-10(11(14)17-12(15)16-9)7-3-5-8(13)6-4-7/h1-10,24-25H,11H2,(H,26,27)(H,28,29);3-6H,2H2,1H3,(H4,14,15,16,17)

HIDE SMILES / InChI

Molecular Formula	C12H13ClN4
Molecular Weight	248.711
Charge	0
Count

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

Molecular Formula	C23H16O6
Molecular Weight	388.3695
Charge	0
Count

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/9554869

Pyrimethamine, sold under the trade name Daraprim, is one of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis. In addition it was approved in Chemoprophylaxis of Malaria. However, resistance to pyrimethamine is prevalent worldwide. It is not suitable as a prophylactic agent for travelers to most areas. Pyrimethamine is well absorbed with peak levels occurring between 2 to 6 hours following administration. It is eliminated slowly and has a plasma half-life of approximately 96 hours. Pyrimethamine is 87% bound to human plasma proteins. Pyrimethamine acts by selectively inhibiting malarial dihydrofolate reductase-thymidylate synthase and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dihydrofolate reductase 57 Target ID: CHEMBL1939 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9554869	Inhibitor 8297		1.5 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Toxoplasmosis 12 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf	Curative	Approved 8429	DARAPRIM Approved Use Treatment of Toxoplasmosis: DARAPRIM is indicated for the treatment of toxoplasmosis when used conjointly with a sulfonamide, since synergism exists with this combination. Treatment of Acute Malaria: DARAPRIM is also indicated for the treatment of acute malaria. It should not be used alone to treat acute malaria. Fast-acting schizonticides such as chloroquine or quinine are indicated and preferable for the treatment of acute malaria. However, conjoint use of DARAPRIM with a sulfonamide (e.g., sulfadoxine) will initiate transmission control and suppression of susceptible strains of plasmodia. Chemoprophylaxis of Malaria: DARAPRIM is indicated for the chemoprophylaxis of malaria due to susceptible strains of plasmodia. However, resistance to pyrimethamine is prevalent worldwide. It is not suitable as a prophylactic agent for travelers to most areas. Launch Date 1953
Acute malaria 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf	Curative	Approved 8429	DARAPRIM Approved Use Treatment of Toxoplasmosis: DARAPRIM is indicated for the treatment of toxoplasmosis when used conjointly with a sulfonamide, since synergism exists with this combination. Treatment of Acute Malaria: DARAPRIM is also indicated for the treatment of acute malaria. It should not be used alone to treat acute malaria. Fast-acting schizonticides such as chloroquine or quinine are indicated and preferable for the treatment of acute malaria. However, conjoint use of DARAPRIM with a sulfonamide (e.g., sulfadoxine) will initiate transmission control and suppression of susceptible strains of plasmodia. Chemoprophylaxis of Malaria: DARAPRIM is indicated for the chemoprophylaxis of malaria due to susceptible strains of plasmodia. However, resistance to pyrimethamine is prevalent worldwide. It is not suitable as a prophylactic agent for travelers to most areas. Launch Date 1953
Malaria 95 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf	Preventing	Approved 8429	DARAPRIM Approved Use Treatment of Toxoplasmosis: DARAPRIM is indicated for the treatment of toxoplasmosis when used conjointly with a sulfonamide, since synergism exists with this combination. Treatment of Acute Malaria: DARAPRIM is also indicated for the treatment of acute malaria. It should not be used alone to treat acute malaria. Fast-acting schizonticides such as chloroquine or quinine are indicated and preferable for the treatment of acute malaria. However, conjoint use of DARAPRIM with a sulfonamide (e.g., sulfadoxine) will initiate transmission control and suppression of susceptible strains of plasmodia. Chemoprophylaxis of Malaria: DARAPRIM is indicated for the chemoprophylaxis of malaria due to susceptible strains of plasmodia. However, resistance to pyrimethamine is prevalent worldwide. It is not suitable as a prophylactic agent for travelers to most areas. Launch Date 1953

C_max

Value	Dose	Co-administered	Analyte	Population
2.059 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8726001	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Zidovudine	Zidovudine	PYRIMETHAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
502.9 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8726001	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Zidovudine	Zidovudine	PYRIMETHAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
190.56 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8726001	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Zidovudine	Zidovudine	PYRIMETHAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
13% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/8578s15lbl.pdf			PYRIMETHAMINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1.625 g single, oral Overdose Dose: 1.625 g Route: oral Route: single Dose: 1.625 g Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 1 n = 1 Health Status: healthy Age Group: 1 Sex: M Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	Disc. AE: Vomiting, Convulsions... AEs leading to discontinuation/dose reduction: Vomiting Convulsions (severe) Cyanosis Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
625 mg single, oral Overdose Dose: 625 mg Route: oral Route: single Dose: 625 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 1 n = 1 Health Status: healthy Age Group: 1 Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	Disc. AE: Convulsions, Respiratory failure... AEs leading to discontinuation/dose reduction: Convulsions Respiratory failure (grade 5) Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
1.2 g single, oral Overdose Dose: 1.2 g Route: oral Route: single Dose: 1.2 g Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: M Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	Disc. AE: Cyanosis, Vomiting... AEs leading to discontinuation/dose reduction: Cyanosis Vomiting (severe) Convulsions Apnoea Haematemesis Cardiac failure (grade 5) Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
400 mg single, oral Overdose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: F Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	Disc. AE: Convulsions, Vomiting... AEs leading to discontinuation/dose reduction: Convulsions (severe) Vomiting Cyanosis Collapse Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
625 mg single, oral Overdose Dose: 625 mg Route: oral Route: single Dose: 625 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 3 n = 1 Health Status: healthy Age Group: 3 Sex: F Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	Disc. AE: Convulsions, Unconsciousness... AEs leading to discontinuation/dose reduction: Convulsions (grade 5) Unconsciousness (grade 5) Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
300 mg single, oral (min) Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Toxoplasmosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3	Disc. AE: Convulsions, Abdominal pain... AEs leading to discontinuation/dose reduction: Convulsions Abdominal pain Nausea Vomiting (severe) Excitability Respiratory depression (grade 5) Circulatory collapse (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3
75 mg 1 times / day multiple, oral (max) Recommended Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Toxoplasmosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.2	Disc. AE: Folate deficiency... AEs leading to discontinuation/dose reduction: Folate deficiency Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.2

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 activator 80	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP1A2 1524 CYP2C19 1478 ALDH1 40 MATE1 306 OCT1 512 OCT2 647 BSEP 402 OATP1B1 788 OATP1B3 706	MRP5 40	CYP1A 56

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDM2In19	inconclusive [Activation 10 uM]
ALDH1 40	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNTc3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDM2In19	inconclusive [Activation 39.8107 uM]
CYP3A4 1925	activator 214 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMzYifX0%3D	inconclusive [Activation 5.0119 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMzYifX0%3D	inconclusive [Activation 7.9433 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMzYifX0%3D	inconclusive [Activation >10 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDM2In19	no [Activation >10 uM]
CYP1A 121	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/12451431/	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDM2In19	no
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22961681/	weak [IC50 200.1 uM]
MATE1 308	inhibitor 3277 Sources: https://go.drugbank.com/drugs/DB00205, https://pubmed.ncbi.nlm.nih.gov/28971610/	yes [IC50 0.131 uM]
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31427432/	yes [IC50 1.8 uM]
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/28971610/	yes [IC50 4.55 uM]
CYP2C8 965	inhibitor 3277 Sources: https://go.drugbank.com/drugs/DB00205, https://pubmed.ncbi.nlm.nih.gov/26721703/	yes [IC50 45.1 uM]
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
MRP5 40	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12869626/	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8673	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8673
ChemicalBook	CB8461315	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8461315
MolPort	MolPort-001-783-655	https://www.molport.com/shop/molecule-link/MolPort-001-783-655
Selleck Chemicals	Pyrimethamine	http://www.selleckchem.com/products/Pyrimethamine.html
ZINC	ZINC000000057464	http://zinc15.docking.org/substances/ZINC000000057464
eMolecules	511729	https://www.emolecules.com/cgi-bin/more?vid=511729

PubMed

Title	Date	PubMed
In vitro cultivation of Cryptosporidium parvum and screening for anticryptosporidial drugs.	1990 Aug	2221857
In vivo assessment of antimicrobial agents against Toxoplasma gondii by quantification of parasites in the blood, lungs, and brain of infected mice.	1990 Aug	2221854
Pneumocystis carinii dihydrofolate reductase used to screen potential antipneumocystis drugs.	1991 Jul	1929292
Evaluation of the effect of drugs on the cyst form of Toxoplasma gondii.	1991 Jul	1647421
Synergistic activity of azithromycin and pyrimethamine or sulfadiazine in acute experimental toxoplasmosis.	1992 May	1324642
Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.	1992 Sep	1416885
The effect of artesunate combined with standard antimalarials against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum in vitro.	1999 Jul-Aug	10674097
Molecular evidence of greater selective pressure for drug resistance exerted by the long-acting antifolate Pyrimethamine/Sulfadoxine compared with the shorter-acting chlorproguanil/dapsone on Kenyan Plasmodium falciparum.	2000 Jun	10837185
Inhibition of growth of Pneumocystis carinii by lactoferrins alone and in combination with pyrimethamine, clarithromycin and minocycline.	2000 Oct	11020255
Anti-toxoplasma activities of antiretroviral drugs and interactions with pyrimethamine and sulfadiazine in vitro.	2000 Sep	10952623
Dapsone-mediated agranulocytosis: risks, possible mechanisms and prevention.	2001 Apr 12	11311458
[Malaria vector control in Cameroon: past, present, future. Reflections].	2001 Jul	16579079
Pitfalls in imaging Hodgkin's disease with computed tomography and positron emission tomography using fluorine-18-fluorodeoxyglucose.	2001 May	11432634
[Adverse effects of Disulone; results of the France pharmacovigilance inquiry. Regional Centers of Pharmacovigilance].	2001 May-Jun	11475811
[Toxoplasmosis in sick persons].	2002	12669554
Hypersensitivity syndrome associated with dapsone/pyrimethamine (Maloprim) antimalaria chemoprophylaxis.	2002 May	12027077
Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro.	2003 Aug	12730611
Effect of immunomodulator daraprim on potentiation of vaccine protection of leishmania major in BALB/c mice.	2003 Mar	17301350
[Disulone].	2004 Dec	15692440
Wellcome home to the Wellcome Foundation Archive.	2004 Jan	14968647
Target guided synthesis of 5-benzyl-2,4-diamonopyrimidines: their antimalarial activities and binding affinities to wild type and mutant dihydrofolate reductases from Plasmodium falciparum.	2004 Jan 15	14711307
Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum.	2004 Jun	15155209
Dapsone hypersensitivity syndrome masquerading as a viral exanthem: three cases and a mini-review.	2004 May	15175785
Pyrimethamine (2,4-diamino-5-p-chlorophenyl-6-ethylpyrimidine) induces apoptosis of freshly isolated human T lymphocytes, bypassing CD95/Fas molecule but involving its intrinsic pathway.	2005 Dec	16157660
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Hydrogen-bonding patterns in pyrimethaminium dinitrate.	2005 Oct	16210764
Research influence on antimalarial drug policy change in Tanzania: case study of replacing chloroquine with sulfadoxine-pyrimethamine as the first-line drug.	2005 Oct 20	16242017
HIV as an additional risk factors for anaemia in pregnancy: evidence from primary care level in Ibadan, Southwestern Nigeria.	2005 Sep	16749361
[Disulone and hepatosiderosis].	2006 Aug-Sep	17053738
[The colorful clinical spectrum of cerebral toxoplasmosis in five HIV positive cases: what comes out of Pandora's box?].	2006 Jan-Apr	16775962
Sulfonamide crystals and acute renal failure.	2006 Jun	16732870
Therapeutic efficacy of sulphadoxine-pyrimethamine and chloroquine for the treatment of uncomplicated malaria in pregnancy in Burkina Faso.	2006 Jun 15	16776817
Presumed dapsone-induced drug hypersensitivity syndrome causing reversible hypersensitivity myocarditis and thyrotoxicosis.	2006 Nov	17160201
Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania.	2006 Oct 31	17076899
Pyrimethamine treatment does not ameliorate lymphoproliferation or autoimmune disease in MRL/lpr-/- mice or in patients with autoimmune lymphoproliferative syndrome.	2007 Dec	17674358
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007 Jan	17003167
Age interactions in the development of naturally acquired immunity to Plasmodium falciparum and its clinical presentation.	2007 Jul 31	17676985
Impact of placental Plasmodium falciparum malaria on pregnancy and perinatal outcome in sub-Saharan Africa: I: introduction to placental malaria.	2007 Jun	18160989
[Acute renal failure due to sulfadiazine crystalluria].	2007 May	17907889
R2(2)(8) motifs in Aminopyrimidine sulfonate/carboxylate interactions: crystal structures of pyrimethaminium benzenesulfonate monohydrate (2:2:1) and 2-amino-4,6-dimethylpyrimidinium sulfosalicylate dihydrate (4:2:2).	2007 Nov 13	17999751
Impact of placental Plasmodium falciparum malaria on pregnancy and perinatal outcome in sub-Saharan Africa: part III: placental malaria, maternal health, and public health.	2008 Mar	18604306
Update on the treatment of ocular toxoplasmosis.	2009	19319237
Potent and specific inhibition of mMate1-mediated efflux of type I organic cations in the liver and kidney by pyrimethamine.	2010 Apr	20065018
Original quinazoline derivatives displaying antiplasmodial properties.	2010 Feb	19926173
Cerebellar toxoplasmosis in HIV/AIDS: a case report.	2010 Mar-Apr	20544640
Palmitate increases the susceptibility of cells to drug-induced toxicity: an in vitro method to identify drugs with potential contraindications in patients with metabolic disease.	2012 Oct	22700542
Identification of a new chemical class of antimalarials.	2012 Sep 1	22732921
Synthesis, characterization and antimalarial activity of quinoline-pyrimidine hybrids.	2013 Jan 1	23168082

Patents

Sample Use Guides

In Vivo Use Guide

Toxoplasmosis: The adult starting dose is 50 to 75 mg of the drug daily, together with 1 to 4 g daily of a sulfonamide of the sulfapyrimidine type, e.g., sulfadoxine. This dosage is ordinarily continued for 1 to 3 weeks, depending on the response of the patient and tolerance to therapy. The dosage may then be reduced to about one half that previously given for each drug and continued for an additional 4 to 5 weeks. The pediatric dosage of DARAPRIM (PYRIMETHAMINE) is 1 mg/kg/day divided into 2 equal daily doses; after 2 to 4 days this dose may be reduced to one half and continued for approximately 1 month. The usual pediatric sulfonamide dosage is used in conjunction with DARAPRIM. Treatment of Acute Malaria: at a dosage of 25 mg daily for 2 days with a sulfonamide will initiate transmission control and suppression of non-falciparum malaria. The adult dosage for acute malaria is 50 mg for 2 days; children 4 through 10 years old may be given 25 mg daily for 2 days. In any event, clinical cure should be followed by the once-weekly regimen described below for chemoprophylaxis. Regimens which include suppression should be extended through any characteristic periods of early recrudescence and late relapse, i.e., for at least 10 weeks in each case. For Chemoprophylaxis of Malaria: Adults and pediatric patients over 10 years — 25 mg (1 tablet) once weekly. Children 4 through 10 years — 12.5 mg (1/2 tablet) once weekly. Infants and children under 4 years — 6.25 mg (1/4 tablet) once weekly.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 18:10:20 GMT 2023` Edited by `admin` on `Fri Dec 15 18:10:20 GMT 2023`
Record UNII	QCT0IT9RPV
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PYRIMETHAMINE PAMOATE

Common Name

English

PYRIMETHAMINE EMBONATE

Common Name

English

2-NAPHTHALENECARBOXYLIC ACID, 4,4'-METHYLENEBIS(3-HYDROXY-, COMP D. WITH 5-(4-CHLOROPHENYL)-6-ETHYL-2,4-PYRIMIDINEDIAMINE

Systematic Name

English

Code System Code Type Description

PUBCHEM

174516

Created by admin on Fri Dec 15 18:10:20 GMT 2023 , Edited by admin on Fri Dec 15 18:10:20 GMT 2023

PRIMARY

FDA UNII

QCT0IT9RPV

Created by admin on Fri Dec 15 18:10:20 GMT 2023 , Edited by admin on Fri Dec 15 18:10:20 GMT 2023

PRIMARY

CAS

85819-86-9

Created by admin on Fri Dec 15 18:10:20 GMT 2023 , Edited by admin on Fri Dec 15 18:10:20 GMT 2023

PRIMARY

EPA CompTox

DTXSID60235098

Created by admin on Fri Dec 15 18:10:20 GMT 2023 , Edited by admin on Fri Dec 15 18:10:20 GMT 2023

PRIMARY

Related Record Type Details


					Z3614QOX8W

PYRIMETHAMINE

PARENT -> SALT/SOLVATE


					7RRQ8QZ38N

PAMOIC ACID

PARENT -> SALT/SOLVATE

Related Record Type Details


					Z3614QOX8W

PYRIMETHAMINE

ACTIVE MOIETY

AE	Significance	Dose	Population
Cyanosis	Disc. AE	1.625 g single, oral Overdose Dose: 1.625 g Route: oral Route: single Dose: 1.625 g Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 1 n = 1 Health Status: healthy Age Group: 1 Sex: M Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Vomiting	Disc. AE	1.625 g single, oral Overdose Dose: 1.625 g Route: oral Route: single Dose: 1.625 g Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 1 n = 1 Health Status: healthy Age Group: 1 Sex: M Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Convulsions	severe Disc. AE	1.625 g single, oral Overdose Dose: 1.625 g Route: oral Route: single Dose: 1.625 g Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 1 n = 1 Health Status: healthy Age Group: 1 Sex: M Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Convulsions	Disc. AE	625 mg single, oral Overdose Dose: 625 mg Route: oral Route: single Dose: 625 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 1 n = 1 Health Status: healthy Age Group: 1 Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Respiratory failure	grade 5 Disc. AE	625 mg single, oral Overdose Dose: 625 mg Route: oral Route: single Dose: 625 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 1 n = 1 Health Status: healthy Age Group: 1 Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Apnoea	Disc. AE	1.2 g single, oral Overdose Dose: 1.2 g Route: oral Route: single Dose: 1.2 g Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: M Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Convulsions	Disc. AE	1.2 g single, oral Overdose Dose: 1.2 g Route: oral Route: single Dose: 1.2 g Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: M Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Cyanosis	Disc. AE	1.2 g single, oral Overdose Dose: 1.2 g Route: oral Route: single Dose: 1.2 g Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: M Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Haematemesis	Disc. AE	1.2 g single, oral Overdose Dose: 1.2 g Route: oral Route: single Dose: 1.2 g Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: M Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Cardiac failure	grade 5 Disc. AE	1.2 g single, oral Overdose Dose: 1.2 g Route: oral Route: single Dose: 1.2 g Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: M Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Vomiting	severe Disc. AE	1.2 g single, oral Overdose Dose: 1.2 g Route: oral Route: single Dose: 1.2 g Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: M Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Collapse	Disc. AE	400 mg single, oral Overdose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: F Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Cyanosis	Disc. AE	400 mg single, oral Overdose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: F Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Vomiting	Disc. AE	400 mg single, oral Overdose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: F Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Convulsions	severe Disc. AE	400 mg single, oral Overdose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 2 n = 1 Health Status: healthy Age Group: 2 Sex: F Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Convulsions	grade 5 Disc. AE	625 mg single, oral Overdose Dose: 625 mg Route: oral Route: single Dose: 625 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 3 n = 1 Health Status: healthy Age Group: 3 Sex: F Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Unconsciousness	grade 5 Disc. AE	625 mg single, oral Overdose Dose: 625 mg Route: oral Route: single Dose: 625 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19	healthy, 3 n = 1 Health Status: healthy Age Group: 3 Sex: F Population Size: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1 Page: p.19
Abdominal pain	Disc. AE	300 mg single, oral (min) Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Toxoplasmosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3
Convulsions	Disc. AE	300 mg single, oral (min) Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Toxoplasmosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3
Excitability	Disc. AE	300 mg single, oral (min) Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Toxoplasmosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3
Nausea	Disc. AE	300 mg single, oral (min) Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Toxoplasmosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3
Circulatory collapse	grade 5 Disc. AE	300 mg single, oral (min) Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Toxoplasmosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3
Respiratory depression	grade 5 Disc. AE	300 mg single, oral (min) Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Toxoplasmosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3
Vomiting	severe Disc. AE	300 mg single, oral (min) Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Toxoplasmosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.3
Folate deficiency	Disc. AE	75 mg 1 times / day multiple, oral (max) Recommended Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Toxoplasmosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf Page: p.2

Details

SMILES

InChI

DescriptionSources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdfCurator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/9554869

CNS Activity

Approval Year

Targets

Conditions

Approved Use

Launch Date

Approved Use

Launch Date

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/9554869

C_max

T_1/2

F_unbound

Drug as perpetrator