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Keywords:

  • Paroxetine;
  • pharmacokinetics;
  • systemic availability;
  • cardiovascular effects;
  • systemic time intervals;
  • man

Abstract: Paroxetine kinetics and cardiovascular effects were studied in 4 healthy male subjects after single oral doses of 45 mg and after slow intravenous infusion of 23–28 mg. The plasma concentration/time curves could be described by a two-compartment open model, but the estimates of the model parameters were relatively inaccurate after the oral test. Plasma half-lives were longer after oral (19.8 hrs, S.D. 1.3 hrs) than after intravenous test (12.3 hrs, S.D. 3.8 hrs). Different methods of calculation of the systemic availability resulted in different values, most probably due to dose dependent kinetics. This is possibly related to saturated elimination kinetics during the first pass metabolism. Systolic time interval measurements showed that paroxetine causes a shortening of the electromechanical systole (QS2 corrected for heart rate) indicating a positive inotropic effect of the compound. Paroxetine also caused a reduction in heart rate and a moderate rise in systolic and diastolic blood pressure. After the intravenous dose some subjects experienced nausea and one subject a quite pronounced anxiety.