Paroxetine: Pharmacokinetics and Cardiovascular Effects after Oral and Intravenous Single Doses in Man

Abstract

Paroxetine [a serotonin uptake inhibitor with antidepressant effects] kinetics and cardiovascular effects were studied in 4 healthy male subjects after single oral doses of 45 mg and after slow i.v. infusion of 23-28 mg. The plasma concentration/time curves could be described by a 2 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 .+-. 1.3 h) than after i.v. test (12.3 .+-. 3.8 h). Different methods of calculation of the systemic availability resulted in different values, probably due to dose-dependent kinetics. This is possibly related to saturated elimination kinetics during the 1st 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 i.v. dose some subjects experienced nausea and 1 subject a pronounced anxiety.