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The plasma pharmacokinetics and tissue distribution of dimethyl sulfoxide in mice
Authors:Thomas S. Kaye  Merrill J. Egorin  Charles E. Riggs  Eve A. Olman  Feng-te E. Chou  Michael Salcman
Affiliation:1. Division of Developmental Therapeutics University of Maryland Cancer Center, USA;2. Neuro-Oncology Service Division of Neurological Surgery University of Maryland School of Medicine 655 West Baltimore Street Baltimore, Maryland 21201, USA
Abstract:We defined the plasma and tissue concentrations and pharmacokinetics of dimethyl sulfoxide (DMSO) in 22–34 g male Swiss Webster mice injected i.v. with 15% DMSO at a dosage of 1.5 mg per g. Concentrations of DMSO in alkalinized, perchloric acid extracts of tissue and plasma were determined by gas-liquid chromatography. Plasma concentrations of DMSO declined in a biexponential fashion that was well described by the equation Ct = 2.36 exp(?0.449 t) + 1.28 exp(?0.00768 t), indicating a t 12 (alpha) of 1.5 min and t 12 (beta) of 90 min. DMSO was rapidly and extensively distributed through tissues and was not concentrated in any particular tissue, although at 1 min after injection, the brain contained the lowest concentration of DMSO of any tissue studied. By 8 hr after injection, there was little DMSO in plasma or any tissue. Intravenous injection of DMSO produced neuro-muscular disturbances, hemolysis, and hemoglobinuria in all animals. Intravenous injection of DMSO produced little increase in plasma osmolality and did not produce any histological evidence of central nervous system of renal tubular damage.
Keywords:To whom reprint requests should be addressed.
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