Clinical pharmacokinetics of lofexidine, the alpha 2-adrenergic receptor agonist, in opiate addicts plasma using a highly sensitive liquid chromatography tandem mass spectrometric analysis.
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.
Yu
Elmer
E
University of Pennsylvania and Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
Miotto
Karen
K
Akerele
Evaristo
E
O'Brien
Charles P
CP
Ling
Walter
W
Kleber
Herbert
H
Fischman
Marian W
MW
Elkashef
Ahmed
A
Herman
Barbara H
BH
Al-Ghananeem
Abeer M
AM
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
D000316:Adrenergic alpha-Agonists; D003000:Clonidine; C025655:lofexidine