PYRIMETHAMINE PHOSPHATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H13ClN4.H3O4P
Molecular Weight	346.707
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OP(O)(O)=O.CCC1=C(C(N)=NC(N)=N1)C2=CC=C(Cl)C=C2

InChI

InChIKey=PILGLRCXWYDHSE-UHFFFAOYSA-N

InChI=1S/C12H13ClN4.H3O4P/c1-2-9-10(11(14)17-12(15)16-9)7-3-5-8(13)6-4-7;1-5(2,3)4/h3-6H,2H2,1H3,(H4,14,15,16,17);(H3,1,2,3,4)

HIDE SMILES / InChI

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
[Pyrimethamine-induced megaloblatic anemia in florid toxoplasmosis].	1976 Feb 13	1256293
Resolution of acute renal failure in toxoplasmic encephalitis despite continuance of sulfadiazine.	1990 Jul-Aug	2385768
In vitro and in vivo effects of doxycycline on Toxoplasma gondii.	1990 May	2360817
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
Activity of minocycline against Toxoplasma gondii infection in mice.	1991 May	1885421
Sulfadiazine-induced crystalluria in AIDS patients with toxoplasma encephalitis.	1991 May	1863412
[Malaria vector control in Cameroon: past, present, future. Reflections].	2001 Jul	16579079
[Toxoplasmosis in sick persons].	2002	12669554
[Therapeutic potential of protein kinase CK2 modulators].	2002	12611170
Antiprotozoals effective in vitro against the scuticociliate fish pathogen Philasterides dicentrarchi.	2002 Jun 3	12113305
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
[Disulone].	2004 Dec	15692440
Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum.	2004 Jun	15155209
Patterns of resistance and DHFR/DHPS genotypes of Plasmodium falciparum in rural Tanzania prior to the adoption of sulfadoxine-pyrimethamine as first-line treatment.	2004 Jun	15099990
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
Sulfadiazine-related obstructive urinary tract lithiasis: an unusual cause of acute renal failure after kidney transplantation.	2005 May	15909603
Malaria in Kenya's western highlands.	2005 Sep	16229773
[The colorful clinical spectrum of cerebral toxoplasmosis in five HIV positive cases: what comes out of Pandora's box?].	2006 Jan-Apr	16775962
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
Suppression of telomerase activity by pyrimethamine: implication to cancer.	2007 Oct	18392083
Update on the treatment of ocular toxoplasmosis.	2009	19319237
Factors related to compliance to anti-malarial drug combination: example of amodiaquine/sulphadoxine-pyrimethamine among children in rural Senegal.	2009 Jun 4	19497103
Antifolate activity of pyrimethamine enhances temozolomide-induced cytotoxicity in melanoma cells.	2009 May	19435820
Self-reported data: a major tool to assess compliance with anti-malarial combination therapy among children in Senegal.	2009 Nov 17	19922609
Active case detection, treatment of falciparum malaria with combined chloroquine and sulphadoxine/pyrimethamine and vivax malaria with chloroquine and molecular markers of anti-malarial resistance in the Republic of Vanuatu.	2010 Apr 6	20370920
Cost effectiveness of seasonal intermittent preventive treatment using amodiaquine & artesunate or sulphadoxine-pyrimethamine in Ghanaian children.	2010 Aug 17	20808923
Images in clinical tropical medicine. Pseudochondritis in leprosy.	2010 Dec	21118916
Turning science into health solutions: KEMRI's challenges as Kenya's health product pathfinder.	2010 Dec 13	21144070
Original quinazoline derivatives displaying antiplasmodial properties.	2010 Feb	19926173
The human proton-coupled folate transporter (hPCFT): modulation of intestinal expression and function by drugs.	2010 Feb	19762432
Cerebellar toxoplasmosis in HIV/AIDS: a case report.	2010 Mar-Apr	20544640
Structure-activity relationships of carbocyclic 6-benzylthioinosine analogues as subversive substrates of Toxoplasma gondii adenosine kinase.	2010 May 15	20456959
Evaluation of the effect of pyrimethamine, an anti-malarial drug, on HIV-1 replication.	2010 Nov	20800626
Pyrimethamine induces oxidative stress in Plasmodium yoelii 17XL-infected mice: a novel immunomodulatory mechanism of action for an old antimalarial drug?	2010 Nov	20193682
Crystal structure of β-hexosaminidase B in complex with pyrimethamine, a potential pharmacological chaperone.	2011 Mar 10	21265544
Antiplasmodial and analgesic activities of Clausena anisata.	2012 Mar	22305787
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
Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target.	2012 Oct 16	23035243
Identification of a new chemical class of antimalarials.	2012 Sep 1	22732921
In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models.	2013	24255594
A new protoberberine alkaloid from Meconopsis simplicifolia (D. Don) Walpers with potent antimalarial activity against a multidrug resistant Plasmodium falciparum strain.	2013 Dec 12	24120516
Male and female Plasmodium falciparum mature gametocytes show different responses to antimalarial drugs.	2013 Jul	23629698
Toxoplasma gondii: the effect of fluconazole combined with sulfadiazine and pyrimethamine against acute toxoplasmosis in murine model.	2013 Mar	23270807
Antimycobacterial activity of nitrogen heterocycles derivatives: bipyridine derivatives. Part III.	2014 Mar 3	24268596

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

Name

Type

Language

PYRIMETHAMINE PHOSPHATE

Common Name

English

PYRIMETHAMINE MONOPHOSPHATE

Common Name

English

2,4-PYRIMIDINEDIAMINE, 5-(4-CHLOROPHENYL)-6-ETHYL-, PHOSPHATE (1:1)

Systematic Name

English

Code System Code Type Description

PUBCHEM

92135840

Created by admin on Fri Dec 15 15:22:54 GMT 2023 , Edited by admin on Fri Dec 15 15:22:54 GMT 2023

PRIMARY

FDA UNII

A4T1033XZA

Created by admin on Fri Dec 15 15:22:54 GMT 2023 , Edited by admin on Fri Dec 15 15:22:54 GMT 2023

PRIMARY

CAS

7681-25-6

Created by admin on Fri Dec 15 15:22:54 GMT 2023 , Edited by admin on Fri Dec 15 15:22:54 GMT 2023

PRIMARY

ACTIVE MOIETY


					Z3614QOX8W

PYRIMETHAMINE

SUBSTANCE RECORD


					A4T1033XZA

PYRIMETHAMINE PHOSPHATE

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