1921
Volume 69, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Atovaquone is a new broad-spectrum antiprotozoal drug with high activity against multidrug-resistant . Its specific action against protozoans is based on the inhibition of the parasite cytochrome complex of the mitochondrial electron transport system. Protozoans may develop atovaquone resistance by the selection of a mutant cytochrome gene. With the increasing availability of atovaquone-proguanil combination for prophylaxis and treatment of malarial infections, it is necessary to establish baseline data on atovaquone sensitivity before the drug is introduced massively in an endemic region. For this purpose, the activity of atovaquone was assessed indirectly by drug sensitivity assays with several serum substitutes and DNA sequencing of the cytochrome gene. Using the standard assay procedures with 10% human serum, the geometric mean 50% inhibitory concentration (IC) for atovaquone was calculated to be 1.15 nM (range = 0.460–4.17 nM), while the use of 10% fetal calf serum resulted in lower ICs (geometric mean = 0.575, range = 0.266–2.20 nM). The use of Albumax, a lipid-enriched bovine albumin, over the same concentration range (0.25–16 nM) showed poor results. None of the 37 isolates with an atovaquone IC < 4.17 nM displayed any mutation. Further monitoring of atovaquone-resistant is warranted for the rational use of this new antimalarial drug.

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2003-08-01
2017-09-23
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  • Received : 07 Sep 2002
  • Accepted : 26 Apr 2003

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