Effect of food on the pharmacokinetics of dronabinol oral solution versus dronabinol capsules in healthy volunteers

Figures & data

Figure 1 Semi-logarithmic mean concentration–time profiles of (A) dronabinol and (B) 11-OH-Δ9-THC for dronabinol oral solution 4.25 mg under fed conditions and dronabinol capsule 5 mg under fed or fasted conditions.

Abbreviation: 11-OH-Δ9-THC, 11-hydroxy-delta-9-tetrahydrocannabinol.

Table 1 Plasma dronabinol pharmacokinetics for dronabinol oral solution 4.25 mg under fed conditions and dronabinol capsule 5 mg under fed or fasted conditions

Parameter	Dronabinol oral solution 4.25 mg (fed state)		Dronabinol capsule 5 mg (fed state)		Dronabinol capsule 5 mg (fasted state)
	Mean (SD)	CV (%)	Mean (SD)	CV (%)	Mean (SD)	CV (%)
Tlag (hour)	0.15 (0.07)a	49.30a	2.02 (1.42)b	70.19b	0.52 (0.55)c	105.17c
Tmax (hour)	7.67 (3.43)a	44.74a	5.59 (3.24)b	57.96b	1.73 (1.74)c	100.82c
Cmax (ng/mL)	1.52 (0.97)a	63.52a	2.60 (1.74)b	67.11b	2.19 (1.06)c	48.51c
AUC0−t (hour × ng/mL)	9.10 (3.84)a	42.20a	10.47 (4.85)b	46.29b	4.44 (2.67)c	60.17c
AUC0−∞ (hour × ng/mL)	10.25 (3.78)d	36.87d	12.21 (4.83)e	39.61e	4.33 (2.49)f	57.52f
t1/2 (hour)	9.35 (6.73)d	71.91d	10.41 (9.24)e	88.72e	4.82 (5.85)f	121.40f

Notes:

a n=52;

b n=54;

c n=53;

d n=30;

e n=35;

f n=47.

Abbreviations: AUC_0−∞, area under the plasma concentration–time curve from time zero to infinity; AUC_0−t, area under the plasma concentration–time curve from time zero to the last measurable concentration; C_max, maximum plasma concentration; CV, coefficient of variation; SD, standard deviation; t_1/2, half-life; T_lag, time to the first measurable concentration; T_max, time to maximum plasma concentration.

Table 2 Plasma 11-OH-Δ9-THC pharmacokinetics for dronabinol oral solution 4.25 mg under fed conditions and dronabinol capsule 5 mg under fed or fasted conditions

Parameter	Dronabinol oral solution 4.25 mg (fed state)a		Dronabinol capsule 5 mg (fed state)b		Dronabinol capsule 5 mg (fasted state)c
	Mean (SD)	CV (%)	Mean (SD)	CV (%)	Mean (SD)	CV (%)
Tlag (hour)	0.20 (0.10)	52.99	1.91 (1.29)	67.75	0.55 (0.56)	100.87
Tmax (hour)	8.50 (3.50)	41.22	5.95 (3.35)	56.38	1.91 (1.15)	60.09
Cmax (ng/mL)	1.23 (0.60)	49.14	2.16 (1.50)	69.58	3.12 (1.67)	53.42
AUC0−t (hour × ng/mL)	12.61 (5.10)	40.44	14.84 (6.48)	43.70	11.17 (6.07)	54.34
AUC0−∞ (hour × ng/mL)	13.29 (5.24)	39.39	15.59 (6.67)	42.77	11.81 (6.18)	52.27
t1/2 (hours)	11.23 (2.97)	26.46	11.11 (2.97)	26.75	12.47 (4.26)	34.18

Notes:

a n=52;

b n=54;

c n=53.

Abbreviations: 11-OH-Δ9-THC, 11-hydroxy-delta-9-tetrahydrocannabinol; AUC_0−∞, area under the plasma concentration–time curve from time zero to infinity; AUC_0−t, area under the plasma concentration–time curve from time zero to the last measurable concentration; C_max, maximum plasma concentration; CV, coefficient of variation; SD, standard deviation; t_1/2, half-life; T_lag, time to the first measurable concentration; T_max, time to maximum plasma concentration.

Figure 2 Percentage of individuals with detectable plasma dronabinol levels (lower level of quantitation, 0.025 ng/mL) through 4 hours postdose for dronabinol oral solution 4.25 mg under fed conditions and dronabinol capsule 5 mg under fed or fasted conditions.

Figure 3 Plasma concentration variability of dronabinol through 4 hours postdose after the administration of dronabinol oral solution 4.25 mg under fed conditions and dronabinol capsule 5 mg under fed conditions.

Note: Dronabinol quantitation range, 0.025–10.0 ng/mL.
Abbreviation: CV, coefficient of variation.

Table S1 ANOVA statistical analyses of pharmacokinetic parameters for dronabinol capsule 5 mg (fed) versus dronabinol capsule 5 mg (fasted)

Variable	Geometric mean
	Dronabinol capsule 5 mg (fed)	Dronabinol capsule 5 mg (fasted)	Ratio (%)a	90% CI	Power	ANOVA CV (%)
ln (Cmax)	2.0903	1.9585	106.73	91.36–124.69	0.7640	51.36
ln (AUC0−t)	9.2884	3.7692	246.43	219.31–276.90	0.9339	37.46
ln (AUC0−∞)	10.9099	3.7779	288.78	248.06–336.20	0.7814	40.72

Note:

a Ratio (%) = geometric mean (dronabinol capsule 5 mg [fed])/geometric mean (dronabinol capsule 5 mg [fasted]).

Abbreviations: ANOVA, analysis of variance; AUC_0−∞, area under the plasma concentration–time curve from time zero to infinity; AUC_0−t, area under the plasma concentration–time curve from time zero to the last measurable concentration; C_max, maximum plasma concentration; CI, confidence interval; CV, coefficient of variation; ln, natural logarithm.

Table S2 ANOVA statistical analyses of pharmacokinetic parameters for dronabinol oral solution 4.25 mg (fed) versus dronabinol capsule 5 mg (fed)

Variable	Geometric mean
	Dronabinol oral solution 4.25 mg (fed)	Dronabinol capsule 5 mg (fed)	Ratio (%)a	90% CI	Power	ANOVA CV (%)
ln (Cmax)	1.2709	2.0903	60.80	51.99–71.10	0.7593	51.36
ln (AUC0−t)	8.2599	9.2884	88.93	79.08–100.00	0.9310	37.46
ln (AUC0−∞)	8.9388	10.9099	81.93	69.00–97.29	0.6905	40.72

Note:

a Ratio (%) = geometric mean (dronabinol oral solution 4.25 mg [fed])/geometric mean (dronabinol capsule 5 mg [fed]).

Abbreviations: ANOVA, analysis of variance; AUC_0−∞, area under the plasma concentration–time curve from time zero to infinity; AUC_0−t, area under the plasma concentration–time curve from time zero to the last measurable concentration; C_max, maximum plasma concentration; CI, confidence interval; CV, coefficient of variation; ln, natural logarithm.

Table S3 ANOVA statistical analyses of pharmacokinetic parameters for dronabinol oral solution 4.25 mg (fed) versus dronabinol capsule 5 mg (fasted)

Variable	Geometric mean
	Dronabinol oral solution 4.25 mg (fed)	Dronabinol capsule 5 mg (fasted)	Ratio (%)a	90% CI	Power	ANOVA CV (%)
ln (Cmax)	1.2709	1.9585	64.89	55.46–75.93	0.7570	51.36
ln (AUC0−t)	8.2599	3.7692	219.14	194.82–246.50	0.9301	37.46
ln (AUC0−∞)	8.9388	3.7779	236.61	201.84–277.37	0.7491	40.72

Note:

a Ratio (%) = geometric mean (dronabinol oral solution 4.25 mg [fed])/geometric mean (dronabinol capsule 5 mg [fasted]).

Abbreviations: ANOVA, analysis of variance; AUC_0−∞, area under the plasma concentration–time curve from time zero to infinity; AUC_0−t, area under the plasma concentration–time curve from time zero to the last measurable concentration; C_max, maximum plasma concentration; CI, confidence interval; CV, coefficient of variation; ln, natural logarithm.