Table 3

Pharmacokinetic parameters of metoprolol and metabolites at each concentration in the absence (control) and presence (AA) of amino acids3-a

Metoprolol Inlet Concentration, μM3.744.495.617.4818.744.9
Metoprolol E
 Control0.73  ± 0.060.72  ± 0.030.69  ± 0.100.62  ± 0.090.39  ± 0.060.28  ± 0.04
 AA0.47  ± 0.083-b 0.47  ± 0.053-b 0.45  ± 0.153-b 0.39  ± 0.083-b 0.20  ± 0.033-b 0.13  ± 0.023-b
Metoprolol F
 Control0.27  ± 0.060.28  ± 0.030.31  ± 0.100.38  ± 0.080.61  ± 0.050.72  ± 0.04
 AA0.53  ± 0.083-b 0.53  ± 0.053-b 0.55  ± 0.153-b 0.61  ± 0.083-b 0.80  ± 0.033-b 0.87  ± 0.023-b
Metoprolol CL (ml/min)
 Control17.3  ± 1.417.2  ± 0.7216.5  ± 2.414.7  ± 2.09.48  ± 1.416.71  ± 0.97
 AA11.1  ± 1.83-b 11.1  ± 1.23-b 10.8  ± 3.53-b 9.23  ± 2.03-b 4.82  ± 0.783-b 3.14  ± 0.483-b
α-Hydroxymetoprolol formationCL (ml/min)
 Control9.55  ± 0.439.48  ± 0.189.58  ± 1.838.87  ± 0.645.66  ± 0.793.62  ± 0.59
 AA6.60  ± 0.713-b 6.85  ± 0.953-b 6.87  ± 2.393-b 5.54  ± 0.463-b 2.53  ± 0.383-b 1.18  ± 0.383-b
O-Demethylmetoprolol formation CL (ml/min)
 Control1.93  ± 0.272.30  ± 0.331.87  ± 0.351.82  ± 0.221.41  ± 0.201.15  ± 0.12
 AA1.83  ± 0.221.90  ± 0.423-b 1.68  ± 0.381.36  ± 0.193-b 0.79  ± 0.113-b 0.58  ± 0.073-b

  • ↵3-a Data reported are means ± SD of four experiments.

  • ↵3-b p < 0.05, control (0–50 min) vs. amino acid coinfusion (50–90 min) by pairedt test.