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Pharmacokinetics and pharmacodynamics of intravenous methylene blue in healthy rhesus monkeys
Author(s) -
TejaIsavadharm P.,
Barker T. L.,
Gettayacamin M.,
Miller R. S.,
Ohrt C. K.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.243
Subject(s) - methylene blue , pharmacokinetics , bioassay , pharmacodynamics , pharmacology , urine , medicine , dosing , feces , in vivo , chemistry , biology , microbiology and biotechnology , biochemistry , photocatalysis , genetics , catalysis
Purpose Methylene blue has antimalarial activity in vitro and in vivo in rats and humans. The purpose of this study is to characterize the pharmacokinetics and pharmacodynamics of intravenous methylene blue in healthy rhesus monkeys. Methods Methylene blue 1% USP solution was administered as a single 30‐second intravenous infusion at doses of 2.5 mg/kg, 5.0 mg/kg and 10.0 mg/kg to healthy rhesus monkeys. Serial venous blood samples were collected at 0, 5, 10, 20, 40, and 60 minutes, and 2, 3 and 5 hours post‐dose. Plasma samples were analyzed for methylene blue concentration by HPLC and total antimalarial activity (by bioassay). Results All monkeys maintained normal clinical signs and symptoms except for blue feces and urine in the 10 mg/kg group for up to 4 days after dosing. The bioassay results for 2.5, 5.0 and 10.0 mg/kg demonstrated respective bioassay AUCs of 79.9, 135.1 and 202.7 μM‐min. There is a linear relationship between bioassay AUC and dose values with an r 2 of >0.9. The HPLC assays of all three doses are pending validation. Conclusions Methylene blue was well tolerated in healthy non‐infected rhesus monkeys, and demonstrated proportional increases in AUC relative to dose. The results of this study will be used to select two different doses of methylene blue to be used in an antimalarial efficacy study of artesunate in combination with methylene blue in a Plasmodium cynomolgi /rhesus monkey model of uncomplicated malaria. Clinical Pharmacology & Therapeutics (2004) 75 , P64–P64; doi: 10.1016/j.clpt.2003.11.243