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

Hypertension induced by serotonin reuptake inhibitors: analysis of two pharmacovigilance databases

“…SRI-induced hypertension remains a controversial topic and only the French SPC of sertraline and paroxetine specify the risk of hypertension. In pre-clinical and phase II-III studies, these two drugs are potentially associated with this risk [19][20][21] unlike the four others [22][23][24][25][26][27]. Finally, those studies were made in normotensive subjects.…”

Oral ketamine for the treatment of pain and treatment-resistant depression

“…It should be noted that interindividual pharmacokinetic variability is common to oral administration in general 48–50 and has also been described for currently prescribed antidepressants. 51 Intranasal and sublingual ketamine administration have been reported to yield 45% and 30% bioavailability, respectively, 23 but interindividual variability has been described for these routes of ketamine administration as well. 52,53 Ketamine absorption after intramuscular injection has been described as more rapid, with a bioavailability of 93%.…”

“…It should be noted that interindividual pharmacokinetic variability is common to oral administration in general [48][49][50] and has also been described for currently prescribed antidepressants. 51 Intranasal and sublingual ketamine administration Overview of daily dose of ketamine for treating pain and number of ketamine days. Thirty-six studies about ketamine used for treating pain were included.…”

Pharmacokinetics of paroxetine, a selective serotonin reuptake inhibitor, in Grey parrots (Psittacus erithacus erithacus): influence of pharmaceutical formulation and length of dosing

“…In addition, electrocardiograms (ECG) were prepared on the day of blood sampling at 0, 2 and 6 h after administration of the paroxetine to study potential cardiovascular side effects. Parameters measured were heart rate and rhythm (including PQ interval length), as previously noted in dogs and humans (Lund et al. , 1982; Yokota et al.…”

“…Paroxetine is a psychoactive drug that is functionally classified as a selective serotonin reuptake inhibitor (SSRI; Lund et al. , 1982; Kaye et al.…”