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British Journal of Anaesthesia, 1985, Vol. 57, No. 11 1085-1088
© 1985 The Board of Management and Trustees of the British Journal of Anaesthesia

research-article

IN VITRO DEGRADATION OF ATRACURIUM IN HUMAN PLASMA

R. L. STILLER, PH.D, D. RYAN COOK, M.D and S. CHAKRAVORTI, PH.D

Departments of Anesthesiology and Psychiatry, University of Pittsburgh School of Medicine Pittsburgh, Pa., USA, 15213.

The degradation of atracurium and the formation of laudanosine was examined in vitro in both Sorensen buffer and human plasma using sensitive, specific high pressure liquid chromato-graphic assays to determine drug concentrations. At normal physiological pH and temperature, the degradation of atracurium was threefold more rapid in plasma than in buffer. Laudanosine is the major end-product of atracurium degradation in buffer or in plasma; its production is more rapid in plasma than in buffer. Dilution of plasma constituents or the use of diisopropylfluorophosphate (a potent esterase inhibitor), slows the degradation of atracurium and the production of laudanosine. We conclude that, although ester hydrolysis is the major metabolic pathway of atracurium degradation. Hofmann elimination provides a "safety net" in its clinical use.


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