Fosmidomycin for the treatment of malaria.
In malaria parasites, isoprenoids are synthesised by the mevalonate independent 1-deoxy- D-xylulose 5-phosphate (DOXP) pathway. Fosmidomycin, a natural antibiotic originally developed for the treatment of bacterial infections, represents an inhibitor of DOXP reductoisomerase, an essential enzyme of this pathway. In recent clinical studies it was shown that fosmidomycin is effective in curing uncomplicated Plasmodium falciparum malaria in humans. The treatment was well tolerated and resulted in a fast parasite and fever clearance. However, the high rate of recrudescence precludes the use of fosmidomycin as a monotherapy. In drug combination studies, synergy of fosmidomycin with clindamycin was observed. Clinical studies with a fosmidomycin-clindamycin combination are currently ongoing.
Wiesner
Jochen
J
Jomaa Pharmaka GmbH, Frankfurter Strasse 50, 35392 Giessen, Germany. Jochen.Wiesner@biochemie.med.uni-giessen.de
Borrmann
Steffen
S
Jomaa
Hassan
H
D000818:Animals; D000962:Antimalarials / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D002981:Clindamycin / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005578:Fosfomycin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D010428:Pentosephosphates / Q000378:metabolism; D010961:Plasmodium / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism; D013729:Terpenes / Q000378:metabolism
C109460:1-deoxylulose 5-phosphate; D000962:Antimalarials; D010428:Pentosephosphates; D013729:Terpenes; D005578:Fosfomycin; D002981:Clindamycin; C024640:fosmidomycin