Synergistic interaction between atovaquone and retinol in Plasmodium falciparum in vitro
Autor: | Walther H. Wernsdorfer, Bettina Exner, Jeeraphat Sirichaisinthop, Gunther Wernsdorfer, Chaiporn Rojanawatsirivet, Herwig Kollaritsch |
---|---|
Rok vydání: | 2007 |
Předmět: |
Plasmodium falciparum
Serum retinol Pharmacology Lethal Dose 50 Antimalarials chemistry.chemical_compound medicine Animals Humans Malaria Falciparum Vitamin A Atovaquone EC50 Dose-Response Relationship Drug biology business.industry Retinol Drug Synergism General Medicine biology.organism_classification In vitro Survival Rate Treatment Outcome chemistry Pharmacodynamics Immunology Standard protocol Drug Therapy Combination business medicine.drug |
Zdroj: | Wiener klinische Wochenschrift. 119:45-52 |
ISSN: | 1613-7671 0043-5325 |
DOI: | 10.1007/s00508-007-0868-2 |
Popis: | The study has been conducted with the objective of assessing the blood schizontocidal activities of atovaquone (ATO), retinol (RET) and combinations of both (ATO-RET) at set retinol concentrations corresponding to the 50th, 65th and 80th percentile of the physiological serum retinol levels. The in vitro tests followed the WHO standard protocol Mark II for measuring the inhibition of schizont maturation in Plasmodium falciparum. Valid results for all 5 test lines were obtained with 26 fresh parasite isolates from northwestern Thailand, an area affected by multidrug-resistance. The EC(50) values for atovaquone, retinol and for ATO in ATO-RET low, medium and high were 3.1 nM, 561.8nM, 0.85 nM, 0.73 nM and 0.45 nM, respectively, the EC(90) values 33.7 nM, 9338.6 nM, 25.31 nM, 8.89 nM, and 5.42 nM. The geometric mean cut-off concentrations of schizont maturation of atovaquone alone and for atovaquone in ATO-RET low, medium and high were 282.5 nM, 79.0 nM, 38.7 nM and 23.7 nM, respectively. These results and those of the Berenbaum analysis based on the fractional inhibitory concentrations indicate synergistic pharmacodynamic interaction between atovaquone and retinol, a phenomenon suggesting that the antimalarial activity of atovaquone could be enhanced by supplementation with retinol. |
Databáze: | OpenAIRE |
Externí odkaz: |
načítá se...