My watch list
my.chemeurope.com  
Login  

Pyrimethamine



Pyrimethamine
Systematic (IUPAC) name
5-(4-chlorophenyl)-6-ethyl-2,4-pyrimidinediamine
Identifiers
CAS number 58-14-0
ATC code P01BD01
PubChem 4993
DrugBank APRD00599
Chemical data
Formula C12H13ClN4 
Mol. mass 248.71 g/mol
Pharmacokinetic data
Bioavailability well-absorbed
Protein binding 87%
Metabolism Hepatic
Half life 96 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

B3(AU) C(US)

Legal status

Prescription only

Routes Oral

Pyrimethamine (Daraprim®) is a medication used for protozoal infections. It is commonly used as an antimalarial drug (for both treatment and prevention), and is also used in the treatment of Toxoplasma gondii infections in immunocompromised patients, such as HIV-positive individuals.

Contents

Mechanism of action

Pyrimethamine interferes with folic acid synthesis by inhibiting the enzyme dihydrofolate reductase. Folic acid is needed for DNA and RNA synthesis in many species, including protozoa.

Mechanism of resistance

Resistance to pyrimethamine is widespread. Mutations in the gene for dihydrofolate reductase may reduce the effectiveness of pyrimethamine (PMID 15155209). These mutations decrease the binding affinity between pyrimethamine and dihydrofolate reductase by steric interactions (PMID 14711307).

Clinical use

Pyrimethamine is typically given with a sulfonamide and folinic acid:

  • Sulfonamides inhibit dihydropteroate synthetase, an enzyme that participates in folic acid synthesis from para-aminobenzoic acid. Hence, sulfonamides work synergistically with pyrimethamine by blocking a different enzyme needed for folic acid synthesis.
  • Folinic acid (Leucovorin) is a compound that can be converted into folic acid by the human body without relying on dihydrofolate reductase. By doing so, folinic acid reduces side effects related to folate deficiency.

Side effects

Pyrimethamine may deplete folic acid in humans, resulting in hematologic side effects associated with folate deficiency.

Side effects include:

  • hypersensitivity reactions
  • megaloblastic anemia
  • leukopenia
  • thrombocytopenia
  • pancytopenia
  • atrophic glossitis
  • hematuria
  • cardiac arrhythmias
  • pulmonary eosinophilia (rare)
  • hyperphenylalaninemia (particularly when used with a sulfonamide)

Contraindications

Pyrimethamine is contraindicated in patients with:

  • hypersensitivity to pyrimethamine
  • megaloblastic anemia - depletion of folic acid may aggravate this condition

References

  • Daraprim - Package insert (PDF file)
  • Fansidar - sulfadoxine and pyrimethamine


 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Pyrimethamine". A list of authors is available in Wikipedia.
Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE