The recently introduced antidepressants, the selective serotonin reuptake inhibitors (SSRIs) [citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline], are known for their clinical efficacy, good tolerability and relative safety. They differ from each other in chemical structure, metabolism and pharmacokinetic properties. Therapeutic drug monitoring of these compounds is not widely used, as the plasma concentration ranges within which clinical response with minimal adverse effects appears to be optimal are not clearly defined. Almost all recent assays developed for the quantitative determination of SSRIs and their metabolites in blood are based either on the separation of SSRIs by high performance liquid chromatography (HPLC) or gas chromatography (GC). Citalopram and fluoxetine have been introduced as racemic compounds. There are some differences in the pharmacological profile, metabolism and pharmacokinetics between the enantiomers of the parent compounds and their demethylated metabolites. Stereoselective chromatographic methods for their analysis in blood are now available. With regard to the SSRIs presently available, no clearcut plasma concentration-clinical effectiveness relationship in patients with depression has been shown, nor any threshold which defines toxic concentrations. This may be explained by their low toxicity and use at dosages where serious adverse effects do not appear. SSRIs vary widely in their qualitative and quantitative interaction with cytochrome P450 (CYP) isozymes in the liver. CYP2D6 is inhibited by SSRIs, in order of decreasing potency paroxetine, norfluoxetine, fluoxetine, sertraline, citalopram and fluvoxamine. This may have clinical consequences with some but not all SSRIs, when they are taken with tricyclic antidepressants. Except for citalopram and paroxetine, little is known about the enzymes which control the biotransformation of the SSRIs. There have been many reports on marked pharmacokinetic interactions between fluoxetine and tricyclic antidepressants. Fluoxetine has a stronger effect on their hydroxylation than on their demethylation. Interactions observed between fluoxetine and alprazolam, midazolam and carbamazepine seem to occur on the level of CYP3A. Fluvoxamine strongly inhibits the N-demethylation of some tricyclic antidepressants of the tertiary amine type and of clozapine. This may lead to adverse effects but augmentation with fluvoxamine can also improve response in very rapid metabolisers, as it increases the bioavailability of the comedication. Fluvoxamine inhibits with decreasing potency, CYP1A2, CYP2C19, CYP2D6 and CYP1A1, but it is also an inhibitor of CYP3A. Fluoxetine and fluvoxamine have shown to increase methadone plasma concentrations in dependent patients. Some authors warn about a combination of monoamine oxidase (MAO) inhibitors with SSRIs, as this could lead to a serotonergic syndrome. Studies with healthy volunteers suggest, however, that a combination of moclobemide and SSRIs, such as fluvoxamine, should not present serious risks in promoting a serotonin syndrome. A combination of moclobemide and fluvoxamine has successfully been used in refractory depression, but more studies are needed, including plasma-concentration monitoring, before this combined treatment can be recommended. Paroxetine is a substrate of CYP2D6, but other enzyme(s) could also be involved. Its pharmacokinetics are linear in poor metabolisers of sparteine, and non-linear in extensive metabolisers. Due to its potent CYP2D6 inhibiting properties, comedication with this SSRI can lead to an increase of tricyclic antidepressants in plasma, as shown with amitriptyline and trimipramine. CYP3A has been claimed to be involved in the biotransformation of sertraline to norsertraline. Clinical investigations (with desipramine) confirmed in vitro findings that CYP2D6 inhibition by sertraline is only moderate. (ABSTRACT TRUNCATED)

Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors.

1. Five drugs with the predominant pharmacologic effect of inhibiting the neuronal reuptake of serotonin are available worldwide for clinical use. This class of psychoactive drugs, known as selective serotonin reuptake inhibitors (SSRIs), is comprised of fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram. 2. The SSRIs appear to share similar pharmacodynamic properties which translate to efficacy in the treatment of depression and anxiety syndromes. The drugs are differentiated by their pharmacokinetic properties with regard to stereochemistry, metabolism, inhibition of cytochrome enzymes, and participation in drug-drug interactions. Studies focusing on the relationship of plasma drug concentration to therapeutic and adverse effects have not confirmed the value of plasma concentration monitoring. 3. This review summarizes the metabolism and relevant pharmacokinetic properties of the SSRIs.

Metabolism and pharmacokinetics of selective serotonin reuptake inhibitors.

Methods for the determination of seven selective serotonin reuptake inhibitors and three active metabolites in human serum using high-performance liquid chromatography and gas chromatography.

Knowledge of the stability of drugs in biological samples is important for the interpretation of toxicological findings. This paper reviews data on the stability of drugs in blood, plasma, or serum. Since such data have already been reviewed for classic drugs of abuse, the focus here is on newer drugs of abuse and on therapeutic drugs. Key information about the conditions of the stability experiments will be provided and the following drugs or drug classes are covered: amphetamines, amphetamine-derived, piperazine-derived, and phenethylamine-derived designer drugs, antidepressants, neuroleptics, anti-HIV drugs, antiepileptics, cardiovascular drugs, and others. In addition, aspects of stability experiments and their evaluations are discussed. The data presented show that the majority of drugs are stable in blood, plasma, or serum samples under the conditions usually encountered in a clinical or forensic toxicology laboratory. Instability usually only occurs for drugs carrying ester moieties, sulfur atoms, or other easily oxidized or reduced structures. Nevertheless, clinical or forensic specimens should always be stored at least in the refrigerator and preferably at −20 °C or lower to avoid any degradation. Finally, results obtained from biosamples that have been stored at room temperature for a longer time should be interpreted with great care and partial degradation should always be considered.

Stability of analytes in biosamples—an important issue in clinical and forensic toxicology?

Analytical methods for the quantitative determination of selective serotonin reuptake inhibitors for therapeutic drug monitoring purposes in patients

Determination of fluoxetine and norfluoxetine in human plasma by capillary gas chromatography with electron-capture detection

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

J. Koons

Author Tools

Chat about Author

Papers

Determination of fluoxetine and norfluoxetine in human plasma by capillary gas chromatography with electron-capture detection