Urine and plasma pharmacokinetics of lofexidine after oral delivery in opiate-dependent patients.
OBJECTIVE
The objective of this study was to investigate lofexidine urine and plasma pharmacokinetics using three different dosing regimens in opioid dependent subjects. To date, there have been no published studies on lofexidine appearance and excretion in urine of opioid dependent subjects.


METHODS
Subjects were stabilized with 100 mg morphine sulphate on days 3-8 of the study. The dosing regimens of lofexidine hydrochloride were .8 mg twice a day (BID), 1.2 mg BID, or .8 mg three times a day (TID) on days 9 through 16 of the study. Plasma and urine samples were collected at appropriate time points. Area under the concentration-time curve (AUC), maximum concentration in plasma (C(max)), time when maximum concentration was reached (T(max)) and fraction excreted unchanged in urine (Fe) were calculated.


RESULTS
The average half-life obtained from all profiles was 12.1 +/- 6.3 hr. Steady-state (SS) was reached by study day 15. The plasma pharmacokinetic parameters for 1.2 mg BID and .8 mg TID dosing regimens did not seem to be different at steady state (day 15). T(max) was not statistically significantly different across dosing regimens. Fe values ranged between .01% and 34% with high variability within the same dosing regimen. For the total dose of 2.4 mg/day the two dosing regimens that were evaluated, namely 1.2 mg BID and .8 mg TID, did not show a significant statistical difference in plasma and urine pharmacokinetic parameters.


CONCLUSIONS
Although preliminary due to the limited number of subjects, these findings are the first to document lofexidine urine pharmacokinetics in opiate addicts using a highly sensitive liquid chromatography tandem mass spectrometric analysis.
Al Ghananeem
Abeer M
AM
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, 40536-0082, USA. amalg0@email.uky.edu
Herman
Barbara H
BH
Abbassi
Maggie
M
Yu
Elmer
E
Miotto
Karen
K
O'Brien
Charles P
CP
Ling
Walter
W
Montgomery
Ann
A
Walsh
Robert
R
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D002853:Chromatography, Liquid; D003000:Clonidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D006207:Half-Life; D006801:Humans; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D010865:Pilot Projects; D053719:Tandem Mass Spectrometry
D009292:Narcotic Antagonists; D003000:Clonidine; C025655:lofexidine