title: Red cell and plasma concentrations of combined quinine-quinidine and quinine in falciparum malaria.
abstract: Red cell and plasma quinine-quinidine, and quinine concentrations in children with uncomplicated falciparum malaria who were treated with a combination of quinine/quinidine/cinchonine (combined drug) and quinine alone, respectively, were measured, using the extraction fluorescence method. The cure rates obtained with the high dose regimen of the combined drug (100%) were significantly higher than in the low dose regimen group (37.5%) (p less than 0.05), and the quinine regimen produced a 50% cure rate. Similar mild and transient ECG effects were noted in both the combined drug group and the quinine group. In patients treated with the combined drug, quinine-quinidine concentrations in both red cell and plasma of the high dose regimen group were significantly higher than those in the low dose regimen group (p less than 0.001, p less than 0.001). In quinine-treated patients, red cell quinine concentration in those with RII failure was significantly lower than that in patients with cure or RI failure (p less than 0.05). Both red cell and plasma levels of quinine-quinidine were higher than quinine levels. The red cell:plasma quinine-quinidine concentration ratios rose steadily to the high level from day 3 to day 6, while the ratio of quinine alone fluctuated around the low level and then gradually fell. The evidence suggests that red cell drug concentrations are more closely related to the outcome of treatment than to plasma concentrations and that the combined drug may be very useful for treatment of multi-drug-resistant P. falciparum infections. Further study is needed.
authors.affiliation: Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: A
authors.initials: A
authors.lastname: Sabchareon
authors.forename: T
authors.initials: T
authors.lastname: Chongsuphajaisiddhi
authors.forename: P
authors.initials: P
authors.lastname: Attanath
authors.forename: V
authors.initials: V
authors.lastname: Singhasivanon
authors.forename: M M
authors.initials: MM
authors.lastname: Acmor-Apolinar
authors.forename: C
authors.initials: C
authors.lastname: Pojjaroen-Anant
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002930:Cinchona Alkaloids / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004341:Drug Evaluation; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy*; D008297:Male; D010949:Plasma / Q000378:metabolism; D011802:Quinidine / Q000097:blood* / Q000627:therapeutic use; D011803:Quinine / Q000097:blood* / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D002930:Cinchona Alkaloids; D004338:Drug Combinations; D011803:Quinine; D011802:Quinidine; C010086:cinchonine