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British Journal of Anaesthesia, 1991, Vol. 66, No. 1 97-102
© 1991 The Board of Management and Trustees of the British Journal of Anaesthesia

research-article

IN VITRO EFFECT OF ADDITIVES IN BENZODIAZEPINE SOLUTIONS ON THE SUPEROXIDE ANION-GENERATING SYSTEM IN POLYMORPHONUCLEAR LEUCOCYTES

H. MORISAKI, M.D., T. TANAKA, M.D., Y. ISHIMURA, M.D., J. TAKEDA, M.D., H. SEKIGUCHI, M.D. and M. NAGANO, M.D.

Department of Anaesthesiology, School of Medicine, Keio University 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan
Department of Biochemistry, School of Medicine, Keio University 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan

Correspondence to H. M.

Inhibitory effects of diazepam and flunitrazepam on the superoxide anion (O2–) -generating system in granulocytes were examined for their clinical relevance. When the effects of commercial solutions and pure preparations were compared using porcine and human polymorphonuclear leucocytes in vitro, the solutions were found to be more inhibitory than the pure drugs by 4–11 times, indicating that inhibition was caused mainly by the additives in the solutions. Concentrations of the additives required for 50% maximal inhibition of the system were 2.3, 7.5 and 0.9 µl ml–1 for propylene glycol, ethanol and benzyl alcohol, respectively, while those of pure diazepam and flunitrazepam were 220 and 190 µg ml–1, respectively, under comparable conditions. However, plasma concentrations of the benzodiazepines and their additives during clinical use were far less than these inhibitory concentrations, indicating that they had no appreciable effect on the O2–-generating system in polymorphonuclear leucocytes of patients.


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