Pharmacokinetics of esomeprazole following intravenous and oral administration in healthy dogs

Figures & data

Figure 1 Median (range) plasma esomeprazole concentration after intravenous (circles) and oral (squares) administration in healthy dogs.

Notes: Median (range) dose administered: intravenous, 1.335 mg/kg (0.93–1.48 mg/kg); oral, 1.35 mg/kg (0.95–1.50 mg/kg).

Table 1 Pharmacokinetic parameters for esomeprazole after single IV bolus and after single po enteric-coated tablet administration in eight healthy dogs

Parameter	Unit	Median IV (range)	Median po (range)
λz	1/min	0.015 (0.011–0.018)	0.01099 (0.0063–0.01575)
t1/2	Minutes	45.56 (39.43–64.20)	63.97 (44.02–109.94)
Tmax	Minutes	2.0 (2.0–2.0)	105 (45–360)
Cmax	μg/mL	4.67 (3.28–6.50)	1.20 (0.45–2.86)
Cmax (dose-normalized)	μg/mL/mg	4.06 (2.47–4.57)	1.04 (0.31–1.91)
AUC0–t	μg/mL*min	314.54 (188.96–406.61)	185.64 (107.095–329.74)
AUC0–∞_obs	μg/mL*min	316.87 (189.19–409.13)	186.99 (123.0–330.78)
AUC0–∞_obs (dose-normalized)	μg/mL*min/mg	246.65 (190.01–354.66)	140.57 (85.57–254.02)
MRT0–∞_obs	Minutes	71.28 (53.36–97.49)	175.85 (123.59–348.28)
F	%	N/A	63.33 (32.26–79.77)
Vz_obs	L/kg	0.27 (0.23–0.34)	N/A
Vz/F_obs	L/kg	N/A	0.64 (0.32–1.33)
Cl_obs	mL/kg/min	4.08 (2.94–5.26)	N/A
Cl/F_obs	mL/kg/min	N/A	7.12 (3.94–11.71)

Notes: t=360 minutes for IV and t=480 minutes for po. Median (range) dose administered for IV was 1.335 mg/kg (0.93–1.48 mg/kg), and was 1.35 mg/kg (0.95–1.50 mg/kg) for po.

Abbreviations: IV, intravenous; po, oral; AUC, area under the curve; MRT, mean residence time; C_max, maximal plasma concentration; T_max, time of C_max; F, po bioavailability; V_z, apparent volume of distribution IV; V_z/F, apparent volume of distribution po; Cl, plasma clearance IV; Cl/F, plasma clearance po; t_1/2, terminal half-life; λ_z, elimination rate constant, N/A, not applicable.

Table 2 Pharmacokinetic parameters for esomeprazole after single oral enteric-coated tablet administration

Parameter	Unit	Minimum	Median	Maximum
λz	1/min	0.00630	0.01099	0.01575
t1/2	Minutes	44.02	63.97	109.94
Tmax	Minutes	45.00	105.00	360.00
Cmax	μg/mL	0.45	1.20	2.86
Cmax(dose-normalized)	μg/mL/mg	0.31	1.04	1.91
AUC0–t	μg/mL*min	107.095	185.64	329.74
AUC0–∞_obs	μg/mL*min	123.00	186.99	330.78
AUC0–∞_obs(dose-normalized)	μg/mL*min/mg	85.42	140.57	254.02
MRT0–∞_obs	Minutes	123.59	175.85	348.28
Vz/F_obs	L/kg	0.32	0.64	1.33
Cl/F_obs	mL/kg/min	3.94	7.12	11.71

Note: t=480 minutes.

Abbreviations: AUC, area under the curve; MRT, mean residence time; C_max, maximal plasma concentration; T_max, time of C_max; V_z/F, apparent volume of distribution; Cl/F, plasma clearance; t_1/2, terminal half-life; λ_z, elimination rate constant.

Figure 2 Median plasma esomeprazole concentration in two groups of healthy dogs after oral administration.

Notes: No lag group (T_max<2 hours; circles) and lag group (T_max≥2 hours; squares). Median (range) dose administered: intravenous, 1.335 mg/kg (0.93–1.48 mg/kg); oral, 1.35 mg/kg (0.95–1.50 mg/kg).