VARIATION IN HUMAN PLASMA CHOLINESTERASE ACTIVITY DURING LOW-DOSE COCAINE ADMINISTRATION

Background: Cocaine is metabolized by a number of enzymes, the activit y of one of which, plasma cholinesterase has been associated with clin ical manifestations of toxicity, Patients with life-threatening compli cations of cocaine intoxication have lower plasma cholinesterase activ ity than less toxic controls, In addition, relatively healthy cocaine users have lower plasma cholinesterase activity than noncocaine using controls, Thus, low plasma cholinesterase activity could be a contribu ting factor to cocaine toxicity, a consequence of cocaine use, or a co nfounding variable, The following study was designed to further assess the relationship between cocaine use and plasma cholinesterase activi ty, Methods: We studied fluctuations in plasma cholinesterase activity in mine subjects enrolled in an inpatient study of the behavioral pha rmacology of smoked cocaine, Subjects used at least 2 g of cocaine wee kly for at least 1 year prior to enrollment, The subjects were admitte d to the research unit where they remained drug-free for 2 days, They then received smoked cocaine for 4 days (up to 405 mg over 5 hours dai ly) and were then drug-free again for 2 days, Plasma cholinesterase ac tivity was measured at 9 AM and 4 PM each day, Results: Baseline plasm a cholinesterase ranged from 265 to 930 U/L (normal > 450 U/L), The me an plasma cholinesterase increased 112 +/- 100 U/L from day 1 to day 8 (p = 0.025), There tvas no daily change in plasma cholinesterase leve ls from 9 AM to 4 PM (15 +/- 165 U/L, p > 0.6), and there was no diffe rence in the daily change between high- and low-dose cocaine days (-3 +/- 137 U/L vs 28 +/- 165 U/L, p = 0.52), Conclusion: These preliminar y data suggest that plasma cholinesterase levels do not change over a 7-hour period as a result of cocaine administration, but may increase during a period of inpatient study, Such are increase could potentiall y influence the pharmacogenetics or effects of cocaine studied in an i npatient setting and may give insight into the etiology of the observe d low-plasma cholinesterase activity in cocaine users.