|Systematic (IUPAC) name|
|AHFS/Drugs.com||Micromedex Detailed Consumer Information|
|By mouth (tablets)|
|Metabolism||By liver (CYP2C19)|
|Metabolites||cycloguanil and 4-chlorophenylbiguanide|
|Biological half-life||12–21 hours|
|ATC code||P01BB01 (WHO)|
|Molar mass||253.731 g/mol|
Proguanil (also known as chlorguanide and chloroguanide) is a prophylactic antimalarial drug. When taken, it is converted to the active metabolite cycloguanil. Proguanil is effective against sporozoites. Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.
It has been used for malarial prophylaxis in children with sickle-cell disease living in malaria-endemic areas for many years.
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.
Atovaquone/proguanil has fewer side effects than mefloquine, but can be more expensive because it is taken daily.
Proguanil is taken with atovaquone for chloroquine-resistant and multidrug resistant strains of P. falciparum and P. vivax. Proguanil combined with atovaquone is sold under the tradename Malarone (GlaxoSmithKline).
General precautions regarding proguanil involve watching out for feelings of sullenness and anxiety to a level outside the ordinary, when taking it over a period of several months. These may come on gradually and may not be immediately attributable to anything in particular.
One mode of action involves cyclization to form cycloguanil, which binds to the dihydrofolate reductase of the parasite and inhibits the folic acid metabolism. However, proguanil itself may have an alternative mechanism of antimalarial action besides dihydrofolate reductase inhibition.
- "Malarone (atovaquone/proguanil) Tablets, Pediatric Tablets. Full Prescribing Information" (PDF). GlaxoSmithKline. Research Triangle Park, NC 27709. Retrieved 14 July 2016.
- Carrington, HC; Crowther, AF; Davey, DG; Levi, AA; Rose, FL (22 December 1951). "A Metabolite of ‘Paludrine’ with High Antimalarial Activity". Nature 168 (4286): 1080. doi:10.1038/1681080a0. PMID 14910643.
- Crowther, AF; Levi, AA (March 1953). "Proguanil—the Isolation of a Metabolite with High Antimalarial Activity". British Journal of Pharmacology and Chemotherapy 8 (1): 93–7. doi:10.1111/j.1476-5381.1953.tb00758.x. PMC 1509229. PMID 13066702. Retrieved 14 July 2016.
- "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- Sutherland, CJ; Laundy, M; Price, N; Burke, M; Fivelman, QL; Pasvol, G; Klein, JL; Chiodini, PL (20 November 2008). "Mutations in the Plasmodium falciparum cytochrome b Gene are Associated with Delayed Parasite Recrudescence in Malaria Patients Treated with Atovaquone-Proguanil". Malaria Journal 7 (1): 240. doi:10.1186/1475-2875-7-240. PMC 2640403. PMID 19021900. Retrieved 14 July 2016.
- Payen, C; Monnin, L; Pulce, C; Descotes, J (March 2010). "Bone Marrow Aplasia Following Acute Poisoning with Chloroquine-Proguanil". Clinical Toxicology 46 (10): 1085–7. doi:10.1080/15563650601182925. PMID 19065311.
- Arfeen, M; Patel, DS; Abbat, S; Taxak, N; Bharatam, PV (30 October 2014). "Importance of Cytochromes in Cyclization Reactions: Quantum Chemical Study on a Model Reaction of Proguanil to Cycloguanil". Journal of Computational Chemistry 35 (28): 2047–55. doi:10.1002/jcc.23719. PMID 25196060.
- Thapar, MM; Gupta, S; Spindler, C; Wernsdorfer, WH; Björkman, A (May 2003). "Pharmacodynamic Interactions Among Atovaquone, Proguanil and Cycloguanil against Plasmodium falciparum in vitro". Transactions of the Royal Society of Tropical Medicine and Hygiene 97 (3): 331–7. doi:10.1016/S0035-9203(03)90162-3. PMID 15228254.