Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine

Abstract

The development of safe, effective and affordable drug combinations against malaria in Africa is a public health priority. Methylene blue (MB) has a similar mode of action as chloroquine (CQ) and has moreover been shown to selectively inhibit the Plasmodium falciparum glutathione reductase. In 2004, an uncontrolled dose-finding study on the combination MB-CQ was performed in 435 young children with uncomplicated falciparum malaria in Burkina Faso (CQ monotherapy had a > 50% clinical failure rate in this area in 2003). Three serious adverse events (SAE) occurred of which one was probably attributable to the study medication. In the per protocol safety analysis, there were no dose specific effects. The overall clinical and parasitological failure rates by day 14 were 10% [95% CI (7.5%, 14.0%)] and 24% [95% CI (19.4%, 28.3%)], respectively. MB appears to have efficacy against malaria, but the combination of CQ-MB is clearly not effective in the treatment of malaria in Africa.

Methylene blue-induced neuronal protective mechanism against hypoxia-reoxygenation stress

“…Methylene blue, the first synthetic drug, has been used in clinics for various diseases for more than a century 22,23,24 . Recently MB has been proposed as a potential treatment for cancer 25 , hepatopulmonary syndrome 26 , and septic shock 27,28 .…”

Quantification of cationic anti-malaria agent methylene blue in different human biological matrices using cation exchange chromatography coupled to tandem mass spectrometry

“…Quantification in urine has been performed using capillary electrophoresis with UV-detection and liquid/liquid extraction with chlorinated organic solvent [18]. To our knowledge liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) has never been applied to MB quantification in biological matrices apart from our previous studies [6,[10][11][12][13]. Chromatography of ionic analytes in general including MB (Fig.…”

“…On the basis of the in vitro results this dosage is expected to yield anti-malarial effectiveness. For dose finding, the evaluation of pharmacokinetics, and the safety of MB co-administered to a typical chloroquine regimen clinical stud- ies were performed [10][11][12][13]. Within these and further studies analytical quantifications of MB were necessary for pharmacokinetic assessment and documentation of compliance.…”

Methylene Blue-Associated Serotonin Syndrome: A ‘Green’ Encephalopathy After Parathyroidectomy

“…After intravenous infusion, it is rapidly accumulated in the parathyroid glands, and animal studies demonstrate rapid CNS accumulation after intravenous administration [11]. Seventy-five percent is excreted by the kidney unchanged, along with its metabolite, leucomethylene, which is reduced from MB via glucose-6 phosphate dehydrogenase (G6PD) [12], and intensely discolors the urine green (Fig. 2) [13] MB is relatively contraindicated in patients with known or suspected G6PD deficiency due to the development of hemolytic anemia [14].…”