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European Journal of Clinical Pharmacology

, Volume 65, Issue 2, pp 179–189 | Cite as

High absolute bioavailability of methylene blue given as an aqueous oral formulation

  • Ingeborg Walter-Sack
  • Jens Rengelshausen
  • Heike Oberwittler
  • Juergen Burhenne
  • Olaf Mueller
  • Peter Meissner
  • Gerd MikusEmail author
Pharmacokinetics and Disposition

Abstract

Purpose

Methylene blue (MB) has recently been reevaluated for malaria treatment. With the aim of excluding treatment failures due to low bioavailability, we have investigated the absolute bioavailability of MB given as an aqueous oral formulation and its interaction with chloroquine (CQ).

Methods

A phase I study in 16 healthy individuals was performed as a monocenter prospective open randomized intra-individual cross-over comparison of MB single doses [50 mg intravenous (i.v.), 500 mg orally, separated by a 1-week wash-out]. After a second week, the group was split for a randomized parallel group comparison of CQ 750 mg administered orally alone or combined with 500 mg MB orally.

Results

Mean MB plasma area under the substrate concentration–time curve (\({\text{AUC}}_{0 - \infty } \)) was 7,639 ± 3,384 ng/mL*h and 51,171 ± 17,147 ng/mL*h after i.v. and oral administration, respectively (dosage 1:10), and 76,897 ± 46,037 ng/mL*h after MB combined with CQ. The absolute bioavailability was 72.3 ± 23.9%. Co-administration with CQ significantly increased MB plasma concentrations (p ≤ 0.016); CQ kinetics remained unaffected.

Conclusion

The absolute bioavailability of MB is high. Co-administration of MB and CQ increases plasma, but not whole blood MB concentrations.

Keywords

Bioavailability Chloroquine Kinetics Methylene blue 

Notes

Acknowledgements

The study was funded by an award from DSM Fine Chemicals Austria, Linz, Austria and by the Deutsche Forschungsgemeinschaft (SFB 544 “Control of Tropical Infectious Diseases” at the Ruprecht-Karls-University Heidelberg). We thank Mrs. Monika Maurer and Mrs. Brigitte Tayrouz for their excellent technical assistance.

Financial disclosure

None of the authors has financial or other relationships that are relevant to the study.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ingeborg Walter-Sack
    • 1
  • Jens Rengelshausen
    • 1
    • 3
  • Heike Oberwittler
    • 1
    • 4
  • Juergen Burhenne
    • 1
  • Olaf Mueller
    • 2
  • Peter Meissner
    • 2
    • 5
  • Gerd Mikus
    • 1
    Email author
  1. 1.Department of Internal Medicine VI, Clinical Pharmacology and PharmacoepidemiologyUniversity HospitalHeidelbergGermany
  2. 2.Department of Tropical Hygiene and Public HealthRuprecht-Karls-UniversityHeidelbergGermany
  3. 3.AachenGermany
  4. 4.ParisFrance
  5. 5.Department of Paediatrics, Department of Tropical Hygiene and Public HealthAIC Kijabe Hospital of Eldoret UniversityEldoretKenya

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