The primary goal of this study is to assess the elimination pharmacokinetics and metabolic disposition of cocaine in a population of chronic cocaine users. Comparisons will be made with historical controls who received single doses of cocaine under experimentally controlled conditions. Secondarily, we will evaluate the usefulness of saliva analysis as an alternative to blood and hair analysis as a measure of historical cocaine use in chronic cocaine users. This study will quantitatively measure, at sequential time-points during a twelve hour period, cocaine and metabolite levels in blood and urine from two groups of adults (18-65 years old) identified as chronic users of large quantities of cocaine. GROUP A subjects will be recruited from an ongoing study at the Archway Clinic, NIDA, IRP. GROUP B will be recruited from the broader population of high-dose cocaine users. This will provide data from which we can measure the elimination of cocaine in this population of chronic users. In addition to blood samples, saliva and hair samples will be collected in order to evaluate their usefulness as a substitute for blood or as historical quantitation of use, respectively. This study will seek to determine whether there is a prolongation of the elimination half-life of cocaine in chronic high-dose cocaine users. Comparison of the metabolite profiles to those of historical controls will indicate whether the prolonged half-life is due to an inhibition of metabolism, secondary to a saturation of the primary enzymatic processes (hydrolysis). Alternately, an extended half-life could be due to accumulation in body tissues, with resultant prolonged elimination. If enzymes are inhibited that are responsible for cocaine's metabolism, this should be reflected by a reduced rate of cocaine elimination from plasma over sequential time points, irrespective of the time of last use, and an increase in the elimination half-life of cocaine. More than one metabolic pathway might be affected if """"""""shunting"""""""" into other metabolic reactions (oxidases) occurs and alterations in ratios of cocaine to metabolites might also be observed.
|Moolchan, E T; Cone, E J; Wstadik, A et al. (2000) Cocaine and metabolite elimination patterns in chronic cocaine users during cessation: plasma and saliva analysis. J Anal Toxicol 24:458-66|