Enzyme Therapy for Surgery-related Apnea

Period of Performance: 03/01/1993 - 08/31/1993

Unknown

Phase 1 SBIR

Recipient Firm

Pharmavene, Inc.
Rockville, MD 20850
Principal Investigator

Abstract

We have developed a method for producing large quantities of highly purified human plasma butyrycholinesterase and will evaluate this enzyme's potential therapeutic value for inactivating both succinylcholine and mivacurium. The muscle relaxant, succinylcholine, is used by anesthesiologists to ease patient intubation and reduce muscle tone in about half of the in-patient surgeries in this country. Mivacurium is a recently developed drug that may replace succinylcholine in many or all of these cases. About 1:2000 individuals are unable to metabolize these compounds due to a deficiency in plasma butyrylcholinesterase and in these patients the period of paralysis and apnea produced by either drug is greatly extended. The hydrolysis of both compounds by butyrylcholinesterase will be quantified in vitro. The reversal of the effects of succinylcholine in rats and mivacurium in cats by butyrylcholinesterase will be measured by EMG. The enzyme will administered i.v. prior to the drug or at the peak of paralysis following the drug. In both cases, butyrylcholinesterase should decrease the effect and/or shorten the time course of either drug. The anticipated results would indicate that exogenous butyrylcholinesterase would effectively relieve prolonged apnea in surgical patients unable to normally metabolize these muscle relaxants.