A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray

被引:77
作者
Stott, C. G. [1 ]
White, L. [1 ]
Wright, S. [1 ]
Wilbraham, D. [2 ]
Guy, G. W. [1 ]
机构
[1] GW Pharma Ltd, Salisbury SP4 0JQ, Wilts, England
[2] Guys Hosp, Quintiles Drug Res Unit, London SE1 9RT, England
关键词
Cannabidiol; Cannabinoid; Delta-9-tetrahydrocannabinol; THC/CBD spray; Spasticity; Sativex; Nabiximols; CANNABINOIDS; TRIAL; PAIN; SCLEROSIS; BLOOD; THC;
D O I
10.1007/s00228-012-1441-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A Phase I study to assess the single and multipledose pharmacokinetics (PKs) and safety and tolerability of oromucosally administered Delta(9)-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, in healthy male subjects. Subjects received either single doses of THC/CBD spray as multiple sprays [2 (5.4 mg THC and 5.0 mg CBD), 4 (10.8 mg THC and 10.0 mg CBD) or 8 (21.6 mg THC and 20.0 mg CBD) daily sprays] or multiple doses of THC/CBD spray (2, 4 or 8 sprays once daily) for nine consecutive days, following fasting for a minimum of 10 h overnight prior to each dosing. Plasma samples were analyzed by gas chromatography-mass spectrometry for CBD, THC, and its primary metabolite 11-hydroxy-THC, and various PK parameters were investigated. Delta(9)-Tetrahydrocannabinol and CBD were rapidly absorbed following single-dose administration. With increasing single and multiple doses of THC/CBD spray, the mean peak plasma concentration (C-max) increased for all analytes. There was evidence of dose-proportionality in the single but not the multiple dosing data sets. The bioavailability of THC was greater than CBD at single and multiple doses, and there was no evidence of accumulation for any analyte with multiple dosing. Inter-subject variability ranged from moderate to high for all PK parameters in this study. The time to peak plasma concentration (T-max) was longest for all analytes in the eight spray group, but was similar in the two and four spray groups. THC/CBD spray was well-tolerated in this study and no serious adverse events were reported. The mean C-max values (< 12 ng/mL) recorded in this study were well below those reported in patients who smoked/inhaled cannabis, which is reassuring since elevated C-max values are linked to significant psychoactivity. There was also no evidence of accumulation on repeated dosing.
引用
收藏
页码:1135 / 1147
页数:13
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