OBJECTIVE: The combination of chloroquine and methylene blue is potentially effective for the treatment of chloroquine-resistant malaria caused by Plasmodium falciparum. The aim of this study was to investigate whether methylene blue influences the pharmacokinetics of chloroquine. METHODS: In a randomized, placebo-controlled, parallel group design, a 3-day course of therapeutic oral doses of chloroquine (total 2.5 g in male, 1.875 g in female participants) withoral co-administration of placebo or 130 mg methylene blue twice daily for 3 days was administered to 24 healthy individuals. Chloroquine, desethylchloroquine, and methylene blue concentrations were determined by means of HPLC/UV orLC/MS/MS assays in whole blood, plasma, and urine for 28 days after the last dose. RESULTS: During methylene blue exposure, the area under the chloroquine whole blood concentration-time curve normalized to body weight (AUC(0-24 h)/BW) yielded a trend of reduction (249+/-98.2 h mug l(-1) kg(-1) versus 315+/-65.0 h mug l(-1) kg(-1), P=0.06). The AUC(0-24 h)/BW of desethylchloroquine was reduced by 35% (104+/-40.3 h mug l(-1) kg(-1) versus 159+/-66.6 h mug l(-1) kg(-1), P=0.03), whereas the metabolic ratio between chloroquine and desethylchloroquine remained unchanged (2.25+/-0.49 versus 1.95+/-0.42, P=0.17). The renal clearance of chloroquine and the ratio between chloroquine in whole blood and plasma remained unchanged (P>0.1). CONCLUSION: Oral co-administration of methylene blue appears to result in a small reduction of chloroquine exposure which is not expected to be clinically relevant and thus represents no concern for further development as an anti-malarial combination.
RCT Entities:
OBJECTIVE: The combination of chloroquine and methylene blue is potentially effective for the treatment of chloroquine-resistant malaria caused by Plasmodium falciparum. The aim of this study was to investigate whether methylene blue influences the pharmacokinetics of chloroquine. METHODS: In a randomized, placebo-controlled, parallel group design, a 3-day course of therapeutic oral doses of chloroquine (total 2.5 g in male, 1.875 g in female participants) with oral co-administration of placebo or 130 mg methylene blue twice daily for 3 days was administered to 24 healthy individuals. Chloroquine, desethylchloroquine, and methylene blue concentrations were determined by means of HPLC/UV or LC/MS/MS assays in whole blood, plasma, and urine for 28 days after the last dose. RESULTS: During methylene blue exposure, the area under the chloroquine whole blood concentration-time curve normalized to body weight (AUC(0-24 h)/BW) yielded a trend of reduction (249+/-98.2 h mug l(-1) kg(-1) versus 315+/-65.0 h mug l(-1) kg(-1), P=0.06). The AUC(0-24 h)/BW of desethylchloroquine was reduced by 35% (104+/-40.3 h mug l(-1) kg(-1) versus 159+/-66.6 h mug l(-1) kg(-1), P=0.03), whereas the metabolic ratio between chloroquine and desethylchloroquine remained unchanged (2.25+/-0.49 versus 1.95+/-0.42, P=0.17). The renal clearance of chloroquine and the ratio between chloroquine in whole blood and plasma remained unchanged (P>0.1). CONCLUSION: Oral co-administration of methylene blue appears to result in a small reduction of chloroquine exposure which is not expected to be clinically relevant and thus represents no concern for further development as an anti-malarial combination.
Authors: O M S Minzi; M Rais; J O Svensson; L L Gustafsson; O Ericsson Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2003-01-15 Impact factor: 3.205
Authors: R Heiner Schirmer; Boubacar Coulibaly; August Stich; Michael Scheiwein; Heiko Merkle; Jana Eubel; Katja Becker; Heiko Becher; Olaf Müller; Thomas Zich; Wolfgang Schiek; Bocar Kouyaté Journal: Redox Rep Date: 2003 Impact factor: 4.412
Authors: C Obua; M Ntale; M S Lundblad; M Mahindi; L L Gustafsson; J W Ogwal-Okeng; W W Anokbonggo; U Hellgren Journal: Afr Health Sci Date: 2006-06 Impact factor: 0.927
Authors: Bina Tariq; Sorina R Simon; Walmari Pilz; Andra Maxim; Bernd Kremer; Laura W J Baijens Journal: Eur Arch Otorhinolaryngol Date: 2021-01-02 Impact factor: 2.503
Authors: Brioni R Moore; Madhu Page-Sharp; Jillian R Stoney; Kenneth F Ilett; Jeffrey D Jago; Kevin T Batty Journal: Antimicrob Agents Chemother Date: 2011-06-06 Impact factor: 5.191
Authors: Kathrin Buchholz; R Heiner Schirmer; Jana K Eubel; Monique B Akoachere; Thomas Dandekar; Katja Becker; Stephan Gromer Journal: Antimicrob Agents Chemother Date: 2007-10-29 Impact factor: 5.191