Inter- and intra-subject variability of metoprolol kinetics after intravenous administration

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Abstract
The pharmacokinetics of metoprolol were assessed from the data of 3 experiments in which intravenous deuterated metoprolol was given concomitantly with various oral metoprolol formulations to healthy volunteers. The plasma levels after intravenous administration were well described by a biexponential equation. However, a deviation from a pure biphasic decline was observed over a short period of time, immediately after the rapid elimination phase. The inter- and intra-subject variability of the parameters describing the two-compartment model was large. The intra-subject variability of the terminal half-life and the plasma clearance was lower than their inter-subject variability. The plasma clearance was linearly related to 1/t1/2. Contrarily to the other parameters of the model, t1/2 appeared to be a characteristic of the subject.