A review of the metabolism and pharmacokinetics of paroxetine in man

@article{Kaye1989ARO,
  title={A review of the metabolism and pharmacokinetics of paroxetine in man},
  author={C. M. Kaye and Rebecca E. Haddock and P. F. Langley and Graham Mellows and T. C. G. Tasker and B. D. Zussman and W. H. Greb},
  journal={Acta Psychiatrica Scandinavica},
  year={1989},
  volume={80}
}
Paroxetine is well absorbed from the gastrointestinal tract, and appears to undergo first‐pass metabolism which is partially saturable. Consistent with its lipophilic amine character, paroxetine is extensively distributed into tissues. Its plasma protein binding at therapeutically relevant concentrations is about 95%. Paroxetine is eliminated by metabolism involving oxidation, methylation, and conjugation. All of these factors lead to wide interindividual variation in the pharmacokinetics of… Expand
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Metoprolol-paroxetine interaction in human liver microsomes: stereoselective aspects and prediction of the in vivo interaction.
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Evaluation of Hepatic Disposition of Paroxetine Using Sandwich-Cultured Rat and Human Hepatocytes
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References

SHOWING 1-10 OF 27 REFERENCES
Evaluation of the potential for interactions of paroxetine with diazepam, cimetidine, warfarin, and digoxin
TLDR
In these studies, paroxetine and the individual interacting drugs were administered repeatedly prior to pharmacokinetic analyses, to achieve distribution equilibrium during the measurement intervals, and plasma levels of warfarin and digoxin were determined in order to assess the effect of parxetine on the steadystate disposition of these agents. Expand
Paroxetine: pharmacokinetics, tolerance and depletion of blood 5-HT in man.
TLDR
The pharmacokinetic studies revealed a dose dependent systemic availability, a rather slow elimination, a good fit to one compartment open model, and an almost complete metabolism of the substance. Expand
The pharmacokinetics of paroxetine in patients with liver cirrhosis
Paroxetine is efficiently absorbed from the gastrointestinal tract. The drug appears to undergo oxidative first-pass metabolism, which is capacity limited and gives rise to non-linearExpand
An overview of the animal pharmacology of paroxetine
  • A. M. Johnson
  • Psychology, Medicine
  • Acta psychiatrica Scandinavica. Supplementum
  • 1989
TLDR
It is concluded that paroxetine should be an effective antidepressant with a reduced propensity to induce the adverse events that are characteristic of the tricyclic class of antidepressants. Expand
Paroxetine: pharmacokinetics and cardiovascular effects after oral and intravenous single doses in man.
TLDR
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. Expand
Paroxetine: pharmacokinetic and antidepressant effect in the elderly
TLDR
Steady‐state, pre‐dose plasma levels of paroxetine showed considerable variability, and the median steady‐state concentration was higher in elderly patients compared with data from a previous study in young volunteers, and elimination half‐lives also showed variability between these elderly patients. Expand
Paroxetine plasma levels: lack of correlation with efficacy or adverse events
TLDR
A retrospective analysis of the available data on the relationship between plasma concentrations of paroxetine and efficacy and adverse events is described. Expand
Metabolic pathway of paroxetine in animals and man and the comparative pharmacological properties of its metabolites
  • R. Haddock, A.M. Johnson, +4 authors F. R. Woods
  • Psychology, Medicine
  • Acta psychiatrica Scandinavica. Supplementum
  • 1989
TLDR
The ability of the predominant metabolites of paroxetine to inhibit the uptake of monoamines into hypothalamic synaptosomes after intravenous administration to rats was investigated. Expand
The pharmacokinetics of paroxetine in elderly depressed patients
  • K. Ghose
  • Medicine
  • Acta psychiatrica Scandinavica. Supplementum
  • 1989
TLDR
Steady-state plasma concentradons are usually reached within 10-14 days of commencing dosing with paroxetine in this population of elderly depressed patients, and the elimination $asma half-life shows wide variability between subjects, but is generally about one day. Expand
The pharmacokinetics of paroxetine in renal impairment
TLDR
Neither the terminal phase rate constant (A,) nor the AUC, correlated well with creatinine clearance, but mean maximum plasma concentrations increased steadily with decreasing renal function, but because of wide inter-subject variability this was not statistically significant. Expand
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