Inter- and intra-subject variability of metoprolol kinetics after intravenous administration.
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.
Richard
J
J
Biopharmaceutical Research Center, Laboratoires Ciba-Geigy, Rueil-Malmaison, France.
Cardot
J M
JM
Godbillon
J
J
D000328:Adult; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008954:Models, Biological; D012189:Retrospective Studies
D003692:Delayed-Action Preparations; D008790:Metoprolol