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

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 (AUC(0-infinity)) 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.