title: Clinical pharmacokinetics of lofexidine, the alpha 2-adrenergic receptor agonist, in opiate addicts plasma using a highly sensitive liquid chromatography tandem mass spectrometric analysis.
abstract: OBJECTIVE
  The objective of this investigation was to characterize the pharmacokinetic profile of lofexidine. Lofexidine is an orally bioavailable alpha 2-adrenergic receptor agonist analogue of clonidine that acts centrally to suppress opiate withdrawal symptoms.
  
  
  METHODS
  During the detoxification period of a phase 3 placebo-controlled, randomized, double-blind trial, six subjects were entered in this preliminary pharmacokinetic study.
  
  
  RESULTS
  Pharmacokinetic analysis of plasma samples collected during study day 7 indicated that C(max) was 3242 +/- 917 ng/L. The mean trough levels between the study days were not significantly different (p > .05), suggesting that the subjects were at steady-state.
  
  
  CONCLUSIONS
  Although preliminary due to the limited number of subjects, these findings are the first to document lofexidine clinical pharmacokinetics in opiate addicts using a highly sensitive liquid chromatography tandem mass spectrometric analysis.
authors.affiliation: University of Pennsylvania and Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
authors.forename: Elmer
authors.initials: E
authors.lastname: Yu
authors.forename: Karen
authors.initials: K
authors.lastname: Miotto
authors.forename: Evaristo
authors.initials: E
authors.lastname: Akerele
authors.forename: Charles P
authors.initials: CP
authors.lastname: O'Brien
authors.forename: Walter
authors.initials: W
authors.lastname: Ling
authors.forename: Herbert
authors.initials: H
authors.lastname: Kleber
authors.forename: Marian W
authors.initials: MW
authors.lastname: Fischman
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elkashef
authors.forename: Barbara H
authors.initials: BH
authors.lastname: Herman
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Al-Ghananeem
mesh_terms: D000284:Administration, Oral; D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000328:Adult; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000379:methods*; D003000:Clonidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004311:Double-Blind Method; D006801:Humans; D009293:Opioid-Related Disorders / Q000534:rehabilitation; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D000316:Adrenergic alpha-Agonists; D003000:Clonidine; C025655:lofexidine