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 Ellen 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… 

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.

Paroxetine: a review of its pharmacology, pharmacokinetics and utility in the treatment of a variety of psychiatric disorders.

  • W. Heydorn
  • Medicine, Psychology
    Expert opinion on investigational drugs
  • 1999
TLDR
The efficacy seen in short-term studies with paroxetine in the treatment of depression is maintained when the drug is given chronically, and the compound shows efficacy superior to placebo, and similar to that obtained with standard tricyclic or tetracyclic agents.

Pharmacokinetics of the newer antidepressants: clinical relevance.

  • C. DeVane
  • Medicine, Biology
    The American journal of medicine
  • 1994

Pharmacokinetics, drug interactions, and tolerability of paroxetine and paroxetine CR.

  • C. DeVane
  • Medicine, Psychology
    Psychopharmacology bulletin
  • 2003
TLDR
Considerations of the pharmacokinetic properties of paroxetine support a rationale for the development of new dosage forms that maintain the efficacy yet improve the tolerability profile of the selective serotonin reuptake inhibitors.

Effect of Potent CYP2D6 Inhibition by Paroxetine on Atomoxetine Pharmacokinetics

TLDR
It was concluded that inhibition of CYP2D6 by paroxetine markedly affected atomxetine disposition, resulting in pharmacokinetics similar to poor metabolizers of CYp2D 6 substrates.

Pharmacokinetic Optimisation of Therapy with Newer Antidepressants

  • P. Goodnick
  • Medicine, Biology
    Clinical pharmacokinetics
  • 1994
TLDR
The antidepressants best suited for pharmacokinetic optimisation of therapy are the following: desipramine, sertraline, fluvoxamine, citalopram and amfebutamone, which stands out as having the best effects on behaviour among all antidepressants.

Terbinafine increases the plasma concentration of paroxetine after a single oral administration of paroxetine in healthy subjects

TLDR
It is demonstrated that the metabolism of paroxetine after a single oral dose was inhibited by terbinafine, suggesting that inhibition of CYP2D6 activity may lead to a change in the pharmacokinetics of paroxin, however, further study is required to confirm this phenomenon at steady state.

Metoprolol-paroxetine interaction in human liver microsomes: stereoselective aspects and prediction of the in vivo interaction.

TLDR
It is shown that paroxetine abolishes the stereoselective metabolism of metoprolol due to a stereoselectedive inhibition of the O-demethylation toward (R)-metoproll.

Pharmacokinetics and pharmacodynamics of the selective serotonin reuptake inhibitors, fluoxetine and paroxetine, during pregnancy and the nursing period

TLDR
In fetal lambs, moderate transient changes in blood gas status were observed following fluoxetine administration, however, in both fluoxettine-exposed human gravida, neither significant changes in birth-outcome nor perinatal complications were observed.
...

References

SHOWING 1-10 OF 24 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.

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.

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-linear

An overview of the animal pharmacology of paroxetine

  • A. M. Johnson
  • Biology, Psychology
    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.

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.

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.

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.

Metabolic pathway of paroxetine in animals and man and the comparative pharmacological properties of its metabolites

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.

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.

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.