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Metabolic Stability of Δ9-Tetrahydrocannabinol in Human Skin Model
Vijay Kumar Shankar, S. Narasimha Murthy
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of
Mississippi, MS-38677
Background and Objective
Δ9-tetrahydrocannabinol (THC) used for treatment of neuropathic pain, when administered via
buccal mucosal or peroral route undergoes extensive first pass metabolism. Intranasal delivery is
associated with great abuse potential, therefore best alternative for drug delivery would be
transdermal route. The aim of this study was to evaluate the in vitro clearance of THC in
cryopreserved human epidermal keratinocytes (HEK). Skin comprises of several enzymes that
could potentially lead to biotransformation of drugs during permeation. Hence, it is required to
investigate the extent of biotransformation of THC in the skin as a prerequisite for considering
development of a transdermal drug delivery system.
Methods
HEK at a 0.5 million cells/well density was incubated with THC or testosterone (positive control)
at 37°C, 5% CO2 for different durations (0, 2, 4, 8 and 24 hours) reaction was terminated and
samples were analyzed by High performance liquid chromatography.
Results
Substrate depletion method was employed for determining intrinsic clearance and half-life by
plotting percentage remaining against time. The intrinsic clearance of Testosterone and THC was
found to be 114 and 15.0 µL/hr/million cells respectively in HEK.
Discussion and Conclusion.
THC have relatively very low clearance on in vitro HEK metabolic stability study. Therefore,
transdermal drug delivery could be considered as a potential route of administration of THC to
achieve constant therapeutic levels over prolonged duration.
Acknowledgement.
This project was made possible by Grant Number P20GM104932 from the National Institute of
General Medical Sciences (NIGMS), a component of the National Institutes of Health (NIH).