Abstract | OBJECTIVES:
Lisdexamfetamine dimesylate (LDX), a long-acting pro-drug psychostimulant, requires conversion to d-amphetamine for therapeutic activity. Conversion of LDX to d-amphetamine occurs primarily in the blood, specifically red blood cells (RBCs). These in vitro studies examine potential conversion in blood-containing pathologically deformed RBCs. METHODS: Fresh blood samples from two human male donors with sickle cell disease and two healthy control donors were incubated for up to 4 h with LDX (1 µg/mL) at 37°C. LDX and d-amphetamine were measured by a validated liquid chromatographic mass spectrometric (LC/MS/MS) method. RESULTS: In incubations of blood from the two donors with sickle cell disease, LDX concentrations declined over time such that 14.1% and 15.3% of initial LDX remained after 4 h. Similarly, in incubations of blood from two healthy donors, LDX concentrations declined over time with 13.1% and 10.5% of initial LDX remaining. Half-life of LDX was 1.30 and 1.36 h for the donors with sickle cell disease and 1.15 and 1.13 h for the healthy donors. Concurrent with the decrease in LDX concentrations, the d-amphetamine concentrations rose in a similar fashion in samples from healthy controls and sickle cell donors. d-Amphetamine levels detected at 4 h with LC/MS/MS were 297.0 ng/mL and 324.3 ng/mL in the two healthy donors and 304.5 ng/mL and 286.6 ng/mL in the two sickle cell donors. CONCLUSIONS: While the current findings are derived from in vitro investigations on a small number of samples and the applicability of this in vitro experimental system to in vivo function has not been established, biotransformation of LDX and the resulting delivery of active d-amphetamine from LDX are likely to be similar in individuals with or without sickle cell disease.
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Authors | Michael Pennick |
Journal | Journal of drug assessment
(J Drug Assess)
Vol. 2
Issue 1
Pg. 17-20
( 2013)
ISSN: 2155-6660 [Print] England |
PMID | 27536433
(Publication Type: Journal Article)
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