Premium
A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects
Author(s) -
Crockett Julie,
Critchley David,
Tayo Bola,
Berwaerts Joris,
Morrison Gilmour
Publication year - 2020
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.16419
Subject(s) - meal , pharmacokinetics , area under the curve , chemistry , cannabidiol , oral administration , zoology , pharmacology , medicine , endocrinology , chromatography , food science , biology , cannabis , psychiatry
Abstract Objective The pharmacokinetics (PK) and safety of single oral 750‐mg doses of a plant‐derived pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex in the USA and Epidyolex in Europe; 100‐mg/mL oral solution) were assessed in healthy adults following a high‐fat/calorie meal (n = 15), a low‐fat/calorie meal (n = 14), whole milk (n = 15), or alcohol (n = 14), relative to the fasted state (n = 29). Methods Blood samples were collected until 96 hours postdose in each period and evaluated by liquid chromatography and tandem mass spectrometry. PK parameters (maximum observed plasma concentration [C max ], area under the plasma concentration‐time curve from time zero to the last observed quantifiable concentration, area under the concentration‐time curve from time zero to infinity [AUC 0‐∞ ], and time to maximum plasma concentration [t max ]) of CBD and its major metabolites were derived using noncompartmental analysis. Results CBD exposure increased by 3.8‐fold for AUC 0‐∞ and 5.2‐fold for C max when CBD was administered with a high‐fat/calorie meal versus fasted. To a lesser extent, a low‐fat/calorie meal enhanced CBD exposure versus fasted with a 2.7‐fold increase in AUC 0‐∞ and a 3.8‐fold increase in C max . Similarly, when dosed with whole milk, CBD exposure increased versus fasted by 2.4‐fold for AUC 0‐∞ and 3.1‐fold for C max . Modest elevations in CBD exposure occurred when it was dosed with alcohol: 1.6‐fold for AUC 0‐∞ and 1.9‐fold for C max . No clinically relevant effect of any test condition on CBD t max or t ½ versus the fasted state was apparent. The same trend was seen for the CBD metabolites, except that 7‐carboxy‐cannabidiol t max was considerably longer when CBD was administered with alcohol (14 vs 4 hours fasted). Inter‐ and intrasubject variability in PK parameters was moderate to high during the trial. Significance CBD and metabolite exposures were most affected by a high‐fat/calorie meal. CBD exposures also increased with a low‐fat/calorie meal, whole milk, or alcohol, but to a lesser extent. CBD was tolerated, and there were no severe or serious adverse events during the trial.