European Journal of Clinical Pharmacology

, Volume 60, Issue 10, pp 709–715

Pharmacokinetic interaction of chloroquine and methylene blue combination against malaria

Authors

  • Jens Rengelshausen
    • Department of Internal Medicine VI, Clinical Pharmacology and PharmacoepidemiologyUniversity of Heidelberg
  • Jürgen Burhenne
    • Department of Internal Medicine VI, Clinical Pharmacology and PharmacoepidemiologyUniversity of Heidelberg
  • Margit Fröhlich
    • Department of Internal Medicine VI, Clinical Pharmacology and PharmacoepidemiologyUniversity of Heidelberg
  • Yorki Tayrouz
    • Department of Internal Medicine VI, Clinical Pharmacology and PharmacoepidemiologyUniversity of Heidelberg
  • Shio Kumar Singh
    • Department of Internal Medicine VI, Clinical Pharmacology and PharmacoepidemiologyUniversity of Heidelberg
    • Division of Pharmacokinetics and MetabolismCentral Drug Research Institute (CDRI)
  • Klaus-Dieter Riedel
    • Department of Internal Medicine VI, Clinical Pharmacology and PharmacoepidemiologyUniversity of Heidelberg
  • Olaf Müller
    • Department of Tropical Hygiene and Public HealthUniversity of Heidelberg
  • Torsten Hoppe-Tichy
    • Hospital PharmacyUniversity of Heidelberg
  • Walter E. Haefeli
    • Department of Internal Medicine VI, Clinical Pharmacology and PharmacoepidemiologyUniversity of Heidelberg
  • Gerd Mikus
    • Department of Internal Medicine VI, Clinical Pharmacology and PharmacoepidemiologyUniversity of Heidelberg
    • Department of Internal Medicine VI, Clinical Pharmacology and PharmacoepidemiologyUniversity of Heidelberg
Pharmacokinetics and Disposition

DOI: 10.1007/s00228-004-0818-0

Cite this article as:
Rengelshausen, J., Burhenne, J., Fröhlich, M. et al. Eur J Clin Pharmacol (2004) 60: 709. doi:10.1007/s00228-004-0818-0

Abstract

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 (AUC0-24 h/BW) yielded a trend of reduction (249±98.2 h μg l−1 kg−1 versus 315±65.0 h μg l−1 kg−1, P=0.06). The AUC0-24 h/BW of desethylchloroquine was reduced by 35% (104±40.3 h μg l−1 kg−1 versus 159±66.6 h μg 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.

Copyright information

© Springer-Verlag 2004