Variation in human plasma cholinesterase activity during low-dose cocaine administration

Background: Cocaine is metabolized by a number of enzymes, the activity of one of which, plasma cholinesterase has been associated with clinical manifestations of toxicity, Patients with life-threatening complications of cocaine intoxication have lower plasma cholinesterase activity 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 contributing factor to cocaine toxicity, a consequence of cocaine use, or a confounding variable, The following study was designed to further assess the relationship between cocaine use and plasma cholinesterase activity. Methods: We studied fluctuations in plasma cholinesterase activity in nine subjects enrolled in an inpatient study of the behavioral pharmacology of smoked cocaine. Subjects used at least 2 g of cocaine weekly for at least 1 year prior to enrollment. The subjects were admitted 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 daily) and were then drug-free again for 2 days. Plasma cholinesterase activity was measured at 9 AM and 4 PM each day, Results: Baseline plasma cholinesterase ranged from 265 to 930 U/L (normal > 450 U/L). The mean plasma cholinesterase increased 112 ± 100 U/L from day 1 to day 8 (p = 0.025). There was no daily change in plasma cholinesterase levels from 9 AM to 4 PM (15 ± 165 U/L, p > 0.6), and there was no difference 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 preliminary 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 an increase could potentially influence the pharmacokinetics or effects of cocaine studied in an inpatient setting and may give insight into the etiology of the observed low-plasma cholinesterase activity in cocaine users.