INTER-SUBJECT AND INTRA-SUBJECT VARIABILITY OF METOPROLOL KINETICS AFTER INTRAVENOUS ADMINISTRATION

The pharmacokinetics of metoprolol were assessed from the data of 3 ex periments in which intravenous deuterated metoprolol was given concomi tantly with various oral metoprolol formulations to healthy volunteers . The plasma levels after intravenous administration were well describ ed by a biexponential equation. However, a deviation from a pure bipha sic decline was observed over a short period of time, immediately afte r the rapid elimination phase. The inter- and intra-subject variabilit y of the parameters describing the two-compartment model was large. Th e intra-subject variability of the terminal half-life and the plasma c learance was lower than their inter-subject variability. The plasma cl earance was linearly related to 1t(1/2). Contrarily to the other param eters of the model, tin appeared to be a characteristic of the subject .