Proguanil
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| Non-proprietary name | Proguanil | ||||||||||||
| other names |
1- (4-chlorophenyl) -5-isopropyl biguanide ( IUPAC ) |
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| Molecular formula | C 11 H 16 ClN 5 | ||||||||||||
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| Molar mass | 253.73 g · mol -1 | ||||||||||||
| Melting point |
129 ° C; Monohydrochloride: 244-245 ° C |
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| pK s value |
2.3; 10.4 |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||
Proguanil is a drug that is used as a monopreparation for chemoprophylaxis and as a combined preparation (with atovaquone ) for chemoprophylaxis and therapy of malaria .
History and Development
Proguanil was developed by Imperial Chemical Industries in the 1940s . At that time, a number of academic and industrial researchers were working on the initiative of the Medical Research Council on the development of new anti-malarial drugs, which were regarded as vital to the war effort. Starting with Atebrin ® (active ingredient: mepacrine ) developed by Bayer AG , around 1700 new substances were synthesized, a third of which were active against malaria. This led to the identification of biguanides as antimalarials. About 200 substances of the biguanides were then tested until proguanil, a substance superior to atebrine, was found. In 1952 the active ingredient was patented by Rhône-Poulenc .
pharmacology
Mode of action
Proguanil is a prodrug that is metabolized in the liver with dehydration to the effective cycloguanil:
An inhibition of the enzyme dihydrofolate reductase of the pathogen Plasmodium falciparum is responsible for the effectiveness of malaria . In the life cycle of the plasmodia , the liver schizonts in particular are inhibited in their development by cycloguanil.
Side effects
Proguanil side effects are rare. Mild stomach discomfort is most common. Allergic reactions have only been reported in isolated cases. In severe renal insufficiency , haematological disorders can occur.
Risk groups and contraindications
Proguanil has been used for decades. No undesirable side effects on mother or fetus could be detected when used during pregnancy. Nevertheless, Proguanil should only be used during pregnancy, especially during the first trimester, after a doctor has assessed the individual risk. Proguanil should be used with caution in patients with acute renal insufficiency.
Dosage and application
Proguanil monopreparations contain 100 mg proguanil hydrochloride per tablet . For malaria prophylaxis, adults take 200 mg daily from one week before the start of the trip to four weeks after the end of the trip. For prophylaxis, Proguanil should always be used in combination with other drugs. Information on resistance in different regions of the world can be obtained through advice from tropical institutes , for example .
Trade names
Paludrine (D)
- in combination with atovaquon : Malarone (D, A, CH)
Individual evidence
- ↑ a b c Entry on Proguanil. In: Römpp Online . Georg Thieme Verlag, accessed on July 25, 2019.
- ↑ a b Proguanil hydrochloride data sheet from Sigma-Aldrich , accessed on April 22, 2011 ( PDF ).
- ^ FHS Curd, F. Rose, Synthetic antimalarials. Part X. Some aryl-diguanide ('biguanide') derivatives. In: J. Chem. Soc. , 1946: 729-737.
- ↑ W. Sneader: Drug Discovery. A history. Wiley 2005 ISBN 0-471-89980-1 .
- ↑ Hans-Dieter Jakubke, Ruth Karcher (coordinators): Lexikon der Chemie in three volumes, Spektrum Verlag, Heidelberg, Volume 3, 1999, ISBN 3-8274-0381-2 , p. 102.
