A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray
A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray
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DOI：
10.1007/s00228-012-1393-4
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发表时间：
2013-04-01
影响因子：
2.9
通讯作者：
Guy, G. W.
中科院分区：
文献类型：
--
作者：
Stott, C. G.;White, L.;Guy, G. W.
To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, when administered to healthy male subjects.Twelve subjects took part in this fed-fasted cross-over study and received a single dose of THC/CBD spray (4 sprays = 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time-points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (C-max) were observed in subjects during fed conditions. Mean AUC and C-max were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The C-max for THC in fed versus fasted subjects was higher in 7 subjects (4.80-14.91 ng/ml) and lower in 5 subjects (2.81-3.51 ng/ml) compared with the mean C-max of 3.98 ng/ml (range 0.97-9.34 ng/ml) observed in the fasted state. Increases in mean AUC((0-t)), AUC((0-inf)), and C-max for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (T-max) of all analytes by approximately 2-2.5 h. Only mild adverse events were reported.The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.
