Intersex and Interspecies Pharmacokinetics of Metoprolol After Oral and Intravenous Dose Administration in Rats and Mice

Figures & data

Table 1. Pharmacokinetic parameters of metoprolol following intravenous dose administration of metoprolol tartrate in Sprague–Dawley rat (n=3; mean ± standard deviation) at 1.0 mg/kg dose.

PK parameters	Metoprolol (iv.; 1 mg/kg of metoprolol tartrate, n = 3)
	Male SD rats	Female SD rats
C0 (ng/ml)	455.345 ± 125.2	463.007 ± 168.3
T1/2 (h)	0.65 ± 0.2	1.03 ± 0.3
Vd (l/kg)	4.215 ± 1.3	8.125 ± 2.4
Cl (ml/min/kg)	76.42 ± 6.4	92.76 ± 11.2
AUClast (h × ng/ml)	215 ± 22.6	180 ± 23.2
AUCinf. (h × ng/ml)	219 ± 18.8	182 ± 23.2
MRTlast (h)	0.67 ± 0.2	0.80 ± 0.2

AUC: Area under the curve; C₀: Plasma drug concentration at T=0; Cl: Plasma drug clearance; iv.: Intravenous; MRT: Mean residence time; PK: Pharmacokinetic; SD: Sprague–Dawley; T_1/2: Elimination half-life; Vd: Volume of distribution.

Figure 1. Concentration–time profile of metoprolol after intravenous dose administration of metoprolol tartrate in male and female rat (n = 3) at 1 mg/kg dose.

mpk: mg/kg.

Table 2. Pharmacokinetic parameters of metoprolol following oral dose administration of metoprolol tartrate in SD rat (n=3; mean ± standard deviation) at 5.0 mg/kg dose.

PK parameters	Metoprolol (oral; 1 mg/kg of metoprolol tartrate, n = 3)
	Male SD rats	Female SD rats
Cmax (ng/ml)	40.981 ± 7.7	270.356 ± 25.4
T1/2 (h)	3.35 ± 0.6	1.342 ± 0.2
Vd_F (lkg)	325.414 ± 78.5	40.479 ± 1.9
ClF (ml/min/kg)	1151.65 ± 332.7	350.07 ± 32.9
AUClast (h × ng/ml)	175 ± 7.9	236 ± 22.3
AUCinf. (h × ng/ml)	NRV ^†	240 ± 23.1
MRTlast (h)	2.00 ± 0.7	1.12 ± 0.2

† NRV: Not reportable value (% extrapolated of total AUC≥120%AUC_0-last).

AUC: Area under the curve; C_max: Maximum plasma drug concentration; Cl_F: Apparent oral clearance; MRT: Mean residence time; PK: Pharmacokinetic; SD: Sprague Dawley; T_1/2: Elimination half-life; Vd_F: Apparent volume of distribution.

Figure 2. Concentration–time profile of metoprolol after oral dose administration of metoprolol tartrate in male and female rat (n = 3) 5 mg/kg dose.

Table 3. Pharmacokinetic parameters of metoprolol following intravenous dose administration of metoprolol tartrate in CD1 mouse (n=3; mean ± standard deviation) at 2.0 mg/kg dose.

PK parameters	Metoprolol (iv.; 2 mg/kg of metoprolol tartrate, n = 3)
	Male CD1 mouse	Female CD1 mouse
C0 (ng/ml)	1144.025 ± 72.3	775.926 ± 154.4
T1/2 (h)	1.13 ± 0.5	1.31 ± 0.5
Vd (l/kg)	3.97 ± 0.8	15.103 ± 4.7
Cl (mL/min/kg)	113.26 ± 12.6	138.42 ± 21.0
AUClast (h × ng/ml)	293 ± 34.6	241 ± 35.2
AUCinf. (h × ng/ml)	297 ± 35.1	244 ± 35.7
MRTlast (h)	0.49 ± 0.1	0.61 ± 0.1

AUC: Area under the curve; C0: Plasma drug concentration at T=0; Cl: Plasma drug clearance; iv.: Intravenous; MRT: Mean residence time; PK: Pharmacokinetic; SD: Sprague–Dawley; T1/2: Elimination half-life; Vd: Volume of distribution.

Figure 3. Concentration–time profile of metoprolol after intravenous dose administration of metoprolol tartrate in male and female mouse (n = 3) at 2 mg/kg dose.

Table 4. Pharmacokinetic parameters of metoprolol following oral dose administration of metoprolol tartrate in CD1 mouse (n=3; mean ± SD) at 10.0 mg/kg dose.

PK parameters	Metoprolol (oral; 10 mg/kg of metoprolol tartrate, n = 3)
	Male CD1 mouse	Female CD1 mouse
Cmax (ng/ml)	878.822 ± 75.5	404.016 ± 113.5
T1/2 (h)	1.55 ± 1.3	1.07 ± 1.0
Vd_F (l/kg)	34.36 ± 22.6	49.13 ± 57.2
ClF (ml/min/kg)	280.60 ± 68.1	457.37 ± 132.9
AUClast (h × ng/ml)	602 ± 133.4	380 ± 118.6
AUCinf. (h × ng/ml)	619 ± 153.9	388 ± 120.8
MRTlast (h)	0.93 ± 0.4	1.17 ± 0.2

AUC: Area under the curve; C0: Plasma drug concentration at T=0; Cl: Plasma drug clearance; iv.: Intravenous; MRT: Mean residence time; PK: Pharmacokinetic; SD: Sprague–Dawley; T1/2: Elimination half-life; Vd: Volume of distribution.

Figure 4. Concentration–time profile of metoprolol after oral dose administration of metoprolol tartrate in male and female mouse (n = 3) at 10 mg/kg dose.

Figure 5. AUC_0-t (systemic exposure) of metoprolol after oral and intravenous dose administration of metoprolol tartrate in male and female rat (n = 3).

AUC: Area under the curve.

Figure 6. AUC_0-t (systemic exposure) of metoprolol after oral and intravenous dose administration of metoprolol tartrate in male and female mouse (n = 3).

AUC: Area under the curve.