Bioavailability of dexlansoprazole delayed-release capsule granules when administered via nasogastric tube or orally via syringe

Figures & data

Table 1 Subject demographics and other baseline characteristics

Characteristics	Sequence of treatment regimens^			All participants N=62
	Sequence ACB N=20	Sequence BAC N=21	Sequence CBAN=21
Age (years)
Mean (SD)	34.5 (10.76)	31.1 (8.91)	33.0 (11.52)	32.9 (10.37)
Median	32.0	29.0	28.0	30.5
Range	18–54	18–53	20–53	18–54
Sex (n, %)
Male	14 (70.0)	14 (66.7)	14 (66.7)	42 (67.7)
Female	6 (30.0)	7 (33.3)	7 (33.3)	20 (32.3)
Hispanic/Latino, n (%)
Yes	0	1 (4.8)	0	1 (1.6)
No	20 (100)	20 (95.2)	21 (100)	61 (98.4)
Race, n (%)
Asian	0	1 (4.8)	3 (14.3)	4 (6.5)
Black/African-American	3 (15.0)	1 (4.8)	3 (14.3)	7 (11.3)
Native Hawaiian/Pacific Islander	0	0	1 (4.8)	1 (1.6)
White	17 (85.0)	19 (90.5)	14 (66.7)	50 (80.6)
BMI (kg/m^2)
Mean (SD)	25.03 (2.688)	24.54 (2.756)	24.51 (3.518)	24.69 (2.976)
Range	20.1–29.5	20.3–29.9	18.4–29.9	18.4–29.9
Smoking classification, n (%)
Never smoked	13 (65.0)	15 (71.4)	71 (81.0)	45 (72.6)
Current smoker	0	0	0	0
Ex-smoker	7 (35.0)	6 (28.6)	4 (19.0)	17 (27.4)
Alcohol classification, n (%)
Never drinks	3 (15.0)	3 (14.3)	2 (9.5)	8 (12.9)
Current drinker	16 (80.0)	17 (81.0)	18 (85.7)	51 (82.3)
Ex-drinker	1 (5.0)	1 (4.8)	1 (4.8)	3 (4.8)
Caffeine consumption, n (%)
Yes	15 (75.0)	15 (71.4)	18 (85.7)	48 (77.4)
No	5 (25.0)	6 (28.6)	3 (14.3)	14 (22.6)
Metabolizer phenotype (CYP2C19), n (%)
Ultrarapid metabolizer	6 (30.0)	9 (42.9)	6 (28.6)	21 (33.9)
Extensive metabolizer	13 (65.0)	12 (57.1)	15 (71.4)	40 (64.5)
Poor metabolizer	1 (5.0)	0	0	1 (1.6)

Notes:

^ Regimen A: dexlansoprazole 60 mg capsule granules mixed with water and administered via NG tube (Test). Regimen B: dexlansoprazole 60 mg capsule granules mixed with water and administered orally via syringe (Test). Regimen C: dexlansoprazole 60 mg capsule, administered intact (Reference).

Abbreviations: BMI, body mass index; CYP2C19, cytochrome P450 2C19 enzyme; NG, nasogastric.

Figure 1 Mean dexlansoprazole plasma concentration–time profiles (linear format) following a single dose of 60 mg dexlansoprazole capsule as the intact capsule or as granules mixed with water and administered via NG tube or orally via syringe.

Abbreviation: NG, nasogastric.

Table 2 Dexlansoprazole pharmacokinetic parameters following administration of dexlansoprazole 60 mg as an aqueous mixture of capsule granules via an NG tube, orally by syringe, or as the intact capsule to healthy participants

tmax a (h), median (min, max)	Cmax (ng/mL) mean (SD)	AUC∞ (ng∙h/mL) mean (SD)	t1/2 (h) mean (SD)	CL/F (L/h) mean (SD)	Vz/F (L) mean (SD)
Dexlansoprazole 60 mg capsule granules via NG tube
n=42	n=42	n=41	n=41	n=41	n=41
5 (1, 8)	997 (576.5)	4,842 (4,848.2)	1.49 (0.79)	17.34 (7.97)	32.30 (13.49)
Dexlansoprazole 60 mg as intact capsule
n=42	n=42	n=41	n=41	n=41	n=41
6 (1, 8)	1,083 (736.1)	5,006 (5,408.0)	1.62 (0.85)	17.77 (8.87)	36.81 (21.72)
Dexlansoprazole 60 mg capsule granules orally via syringe
n=50	n=50	n=47	n=47	n=47	n=47
5.5 (0.5, 7)	1,014 (492.0)	4,887 (4,448.8)	1.77 (1.02)	16.75 (7.53)	40.31 (33.44)
Dexlansoprazole 60 mg as intact capsule
n=50	n=50	n=47	n=47	n=47	n=47
6 (1, 8)	1,061 (696.4)	4,944 (5,079.9)	1.67 (0.84)	17.47 (8.61)	37.50 (20.95)

Notes:

a Median (minimum–maximum) reported for t_max. Because of variability in the terminal phase of the plasma concentration–time curve, the terminal elimination rate constant could not be determined for some subjects, and therefore, the pharmacokinetic parameters that use this constant in their calculations (ie, t_1/2, AUC_∞, CL/F, and V_z/F) could not be estimated.

Abbreviations: AUC_∞, area under the plasma concentration–time curve from time 0 to infinity; CL/F, apparent clearance after oral administration; C_max, maximum observed concentration; NG, nasogastric; t_1/2, terminal elimination half-life; t_max, time to first occurrence of C_max; V_z/F, apparent volume of distribution after oral administration.

Table 3 Statistical comparisons of pharmacokinetic parameter estimates for dexlansoprazole following administration of dexlansoprazole 60 mg as an aqueous mixture of capsule granules via NG tube or orally via syringe, or as the intact capsule to healthy participants

Parameter	Point estimate of the relative bioavailability	90% CIs for the point estimate
NG tube administration (test) vs intact capsule (reference)
Cmax (N=42/50)	0.9855	(0.8939–1.0864)
AUC∞ (N=41/49)	1.0077	(0.9523–1.0663)
Oral syringe administration (test) vs intact capsule (reference)
Cmax (N=50/50)	0.9932	(0.9059–1.0890)
AUC∞ (N=47/49)	1.0172	(0.9638–1.0736)

Notes: N = (Test/Reference). The participants with valid estimates for intact capsule regimen and at least 1 other regimen were included in the analysis for that parameter.

Abbreviations: AUC_∞, area under the plasma concentration–time curve from time 0 to infinity; C_max, maximum observed concentration; NG, nasogastric.

Table 4 TEAEs, including SAEs

Events	Dexlansoprazole 60 mg			Overall N=62
	NG tube administration N=49	Oral syringe administration N=60	Oral intact capsule N=52
Participants with any TEAEs, n (%)	12 (24.5)	10 (16.7)	12 (23.1)	28 (45.2)
Total events	19	22	19	60
Related	0	4	3	7
Not related	19	18	16	53
Mild	19	20	19	58
Moderate	0	2	0	2
Severe	0	0	0	0
Participants with TEAEs leading to study drug discontinuation, n (%)	0	1 (1.7)	0	1 (1.6)
Participants with SAEs, n (%)	0	0	0	0
Participants who died, n (%)	0	0	0	0

Notes: A TEAE was defined as an AE whose date of onset occurred after the first dose of study drug and within 30 days after the last dose of study drug. Percentages were based on the number of participants in the safety set for each treatment group. Medical Dictionary for Regulatory Activities (MedDRA) Version 15.0 was used for coding AEs.

Abbreviations: AE, adverse event; NG, nasogastric; SAE, serious adverse events; TEAE, treatment-emergent adverse event.

Figure S1 Mean (±SD) plasma concentration–time plots (linear format) for dexlansoprazole following administration of dexlansoprazole 60 mg as an aqueous mixture of capsule granules via an NG tube or as an intact capsule to healthy subjects.

Abbreviation: NG, nasogastric.

Figure S2 Mean (±SD) plasma concentration–time plots (linear format) for dexlansoprazole following administration of dexlansoprazole 60 mg as an aqueous mixture of capsule granules via an oral syringe or as an intact capsule to healthy subjects.