Clinical Pharmacokinetics of Selective Serotonin Reuptake Inhibitors

  title={Clinical Pharmacokinetics of Selective Serotonin Reuptake Inhibitors},
  author={Jaap van Harten},
  journal={Clinical Pharmacokinetics},
  • J. Harten
  • Published 1 March 1993
  • Medicine, Biology, Psychology
  • Clinical Pharmacokinetics
SummaryA feature common to all selective serotonin reuptake inhibitors (SSRIs) is that they are believed to act as antidepressant drugs because of their ability to reversibly block the reuptake of serotonin (5-hydroxytryptamine; 5-HT) in the synaptic cleft. From a chemical perspective, however, they show distinct differences. Consequently, the pharmacokinetic behaviour of the drugs can be very different, and these pharmacokinetic differences may have a major influence on their clinical profiles… 

Clinically Relevant Pharmacology of Selective Serotonin Reuptake Inhibitors

  • S. Preskorn
  • Medicine, Biology
    Clinical pharmacokinetics
  • 1997
An overview of the clinically relevant pharmacology of selective serotonin reuptake inhibitors (SSRIs) with an emphasis on their pharmacokinetics and effects on cytochrome P450 (CYP) enzymes is presented.

Interactions of serotonin reuptake inhibitors with tricyclic antidepressants.

It is found that several SRIs can interfere with the activity of a major drug-metabolizing pathway, the human hepatic microsomal cytochrome P-450-2D6 isozyme, in vitro, and in vitro data are suggestive of clinical studies of the effects of SRIs other than fluoxetine on TCA metabolism.

Selective serotonin reuptake inhibitors in affective disorders — I. Basic pharmacology

There are important clinical differences among the SSRIs in their pharmacokinetic characteristics including differences in their half-lives, linear versus non-linear pharmacokinetics, effect of age on their clearance and their potential to inhibit drug metabolising cytochrome P450 (CYP) isoenzymes.

Pharmacokinetics of selective serotonin reuptake inhibitors.

Pharmacokinetic-Pharmacodynamic Relationship of the Selective Serotonin Reuptake Inhibitors

  • P. Baumann
  • Medicine, Biology
    Clinical pharmacokinetics
  • 1996
No clearcut plasma concentration-clinical effectiveness relationship in patients with depression has been shown, nor any threshold which defines toxic concentrations, and SSRIs presently available may be explained by their low toxicity and use at dosages where serious adverse effects do not appear.

Pharmacokinetics of selective serotonin reuptake inhibitors: clinical relevance.

Knowing about pharmacokinetic profiles of SSRIs will enable clinicians to predict and make appropriate dose adjustments to avoid potential drug-drug interactions that otherwise could result in toxicity.

Drug Interactions of Clinical Significance with Selective Serotonin Reuptake Inhibitors

This article details those medications that may interact significantly with the SSRIs, and provides clinical guidelines for minimising the likelihood of such complications.

Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review

The pharmacogenetics of the selective serotonin reuptake inhibitors

  • K. Brøsen
  • Biology, Chemistry
    The clinical investigator
  • 2004
Citalopram and fluoxetine are administered as racemates, but practically nothing is known about the stereoselective metabolism of the two drugs.

SSRI differentiation: Pharmacology and pharmacokinetics

  • B. Leonard
  • Biology, Medicine
    Human psychopharmacology
  • 1995
Differences in potency at inhibiting serotonin reuptake and the suitability of individual SSRIs in special patient groups are apparent and it is worthwhile to be made aware of possible interactions between drugs that act as inhibitors or substrates of the hepatic cytochrome P450 system.



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Preliminary data suggest that citalopram may be particularly useful in patients who cannot tolerate the anticholinergic or cardiovascular side effects of tricyclic antidepressants and in those for whom sedation is not indicated.

Fluoxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness.

Fluoxetine has overall therapeutic efficacy comparable with imipramine, amitriptyline and doxepin in patients with unipolar depression treated for 5 to 6 weeks, although it may be less effective than tricyclic antidepressants in relieving sleep disorders in depressed patients.

Selective Serotonin Re-Uptake Inhibitors: The Clinical Use of Citalopram, Fluoxetine, Fluvoxamine, Paroxetine, and Sertraline

The neuropharmacology of serotonin in the central nervous system, C.A.Marsden the comparative pharmacological properties of selective serotonin re-uptake inhibitors in animals, A.M.Johnson the

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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 pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness.

Overall, available data appear to indicate that while the efficacy of paroxetine is similar to that of traditional antidepressant drugs, the newer agent possesses much improved tolerability and may be beneficial when treating patients with an increased risk of suicide.

The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes.

It is suggested that compounds with SSRI activity are likely to interact with human CYP2D6 in vivo with the potential of causing drug interactions.

Fluoxetine disposition and elimination in cirrhosis

It is shown that in stable alcoholic cirrhosis, the elimination of fluoxetine is significantly reduced and the formation of norfluoxETine was decreased and its clearance was also reduced, meaning that at steady state both fluoxettine and norfluxetine concentrations will be higher in patients with cirrhotic disease, unless the dosage is reduced.

Inhibition of serotonin uptake by optical isomers of fluoxetine

The optical isomers of fluoxetine, a selective inhibitor of serotonin (5‐hydroxytryptamine, 5HT) uptake, have been compared pharmacologically and the (−)‐isomer had a much shorter duration of action than the (+)‐ isomer in rats.

Clinical Pharmacology and Pharmacokinetics of Fluoxetine: A Review

This paper reviews the published information relevant to fluoxetine's pharmacology and pharmacokinetics in man and describes it as one of the first selective serotonin uptake inhibitors.