title: In-vitro interaction of tafenoquine and chloroquine in Plasmodium falciparum from northwestern Thailand.
abstract: The blood schizontocidal, pharmacodynamic interaction between tafenoquine (WR 238605--a 5-phenoxyprimaquine derivative--and chloroquine was investigated, using an in-vitro test for the inhibition of schizont maturation, in 15 fresh isolates of Plasmodium falciparum that originated from northwestern Thailand and neighbouring Myanmar. In this area the parasite is highly resistant to chloroquine. The geometric mean cut-off concentrations of schizont maturation for tafenoquine and chloroquine were 5261 nM and 7638 nM, respectively. With a mixture of tafenoquine and chloroquine, the mean cut-off concentration was 5252 nM, corresponding to 389 nM tafenoquine + 4863 nM chloroquine. Further analysis showed that the interaction between tafenoquine and chloroquine was additive within the range of EC20 and EC77. At concentrations higher than the EC77, interaction was moderately synergistic. While tafenoquine did not reverse the resistance to chloroquine to the degree of clinically relevant sensitivity, there was evidence that the blood schizontocidal efficacy of tafenoquine would be enhanced in the presence of chloroquine.
authors.affiliation: Department of Medical Microbiology, Institute of Hygiene, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Vollnberg
authors.forename: Somsak
authors.initials: S
authors.lastname: Prajakwong
authors.forename: Jeeraphat
authors.initials: J
authors.lastname: Sirichaisinthop
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wiedermann
authors.forename: Gunther
authors.initials: G
authors.lastname: Wernsdorfer
authors.forename: Walther H
authors.initials: WH
authors.lastname: Wernsdorfer
mesh_terms: D000293:Adolescent; D000328:Adult; D000634:Aminoquinolines / Q000008:administration & dosage*; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects; D002738:Chloroquine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004341:Drug Evaluation / Q000379:methods; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood* / Q000188:drug therapy / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000145:classification / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D013045:Species Specificity; D013785:Thailand
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D004338:Drug Combinations; C055852:tafenoquine; D002738:Chloroquine