Retrospective Pilot Study for Analysis of Antidepressant Serum Concentrations of Citalopram and Venlafaxine during Inflammation

Hefner, Gudrun; Shams, Maher; Unterecker, Stefan; Falter, Tanja; Hiemke, Christoph

doi:10.1055/s-0035-1559666

Cited by 7 publications

(11 citation statements)

References 24 publications

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“…Other authors have also suggested that acute inflammation does not impact on CYP2D6 activity, as well as diabetes (type I, type II, and gestational). 32,33,[44][45][46] In a study conducted in patients with congestive heart failure, TNF-α and IL-6 levels were furthermore not associated with CYP2D6 activity. 29 However, another study showed that CYP2D6 activity (mean urinary dextromethorphan ratio for 4 consecutive days) was significantly higher in HIV-infected patients than in healthy volunteers.…”

Section: Discussionmentioning

confidence: 96%

“…We described that CYP2D6 activity did not change significantly in the first 3 days after surgery, but a trend for a 50% decrease was noted at discharge, and inversely correlated with surgery and TNF‐α levels. Other authors have also suggested that acute inflammation does not impact on CYP2D6 activity, as well as diabetes (type I, type II, and gestational) 32,33,44–46 . In a study conducted in patients with congestive heart failure, TNF‐α and IL‐6 levels were furthermore not associated with CYP2D6 activity 29 .…”

Section: Discussionmentioning

confidence: 97%

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Impact of Acute Inflammation on Cytochromes P450 Activity Assessed by the Geneva Cocktail

Lenoir

Daali

Rollason

et al. 2021

Clin Pharma and Therapeutics

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Cytochromes P450 (CYP) are subject to important interindividual variability in their activity due to genetic and environmental factors and some diseases. Limited human data support the idea that inflammation downregulates CYP activities. Our study aimed to evaluate the impact of orthopedic surgery (acute inflammation model) on the activity of six human CYP. This prospective observational study was conducted in 30 patients who underwent elective hip surgery at the Geneva University Hospitals in Switzerland. The Geneva phenotyping cocktail containing caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, and midazolam as probe drugs respectively assessing CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A activities was administered orally before surgery, day 1 (D1) and 3 (D3) postsurgery and at discharge. Capillary blood samples were collected 2 hours after cocktail intake to assess metabolic ratios (MRs). Serum inflammatory markers (CRP, IL-6, IL-1β, TNF-α, and IFN-γ) were also measured in blood. CYP1A2 MRs decreased by 53% (P < 0.0001) between baseline and the nadir at D1. CYP2C19 and CYP3A activities (MRs) decreased by 57% (P = 0.0002) and 61% (P < 0.0001), respectively, with the nadir at D3. CYP2B6 and CYP2C9 MRs increased by 120% (P < 0.0001) and 79% (P = 0.018), respectively, and peaked at D1. Surgery did not have a significant impact on CYP2D6 MR. Hip surgery was a good acute inflammation model as CRP, IL-6, and TNF-α peak levels were reached between D1 and day 2 (D2). Acute inflammation modulated CYP activity in an isoform-specific manner, with different magnitudes and kinetics. Acute inflammation may thus have a clinically relevant impact on the pharmacokinetics of these CYP substrates.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 97%

Impact of Acute Inflammation on Cytochromes P450 Activity Assessed by the Geneva Cocktail

Lenoir

Daali

Rollason

et al. 2021

Clin Pharma and Therapeutics

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“…By contrast, no impact of the CRP value was observed on the pharmacokinetics of quetiapine in the same study. Concerning antidepressant drugs, one retrospective comparative study showed that the CRP concentration was not associated with the pharmacokinetics of citalopram or venlafaxine ( Hefner, Shams, 2015 ; Hiemke et al, 2018 ). These results confirm a different impact of inflammation on psychotropic drug metabolism depending on the CYP isoform and their respective contribution in the drug clearance.…”

Section: Pharmacological Consequences Of Acute Inflammation-induced Mmentioning

confidence: 99%

Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment

Stanke‐Labesque

Gautier-Veyret

Chhun

et al. 2020

Pharmacology & Therapeutics

120

147

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Inflammation is an evolutionary process that allows survival against acute infection or injury. Inflammation is also a pathophysiological condition shared by numerous chronic diseases. In addition, inflammation modulates important drug-metabolizing enzymes and transporters (DMETs), thus contributing to intra- and interindividual variability of drug exposure. A better knowledge of the impact of inflammation on drug metabolism and its related clinical consequences would help to personalize drug treatment. Here, we summarize the kinetics of inflammatory mediators and the underlying transcriptional and post-transcriptional mechanisms by which they contribute to the inhibition of important DMETs. We also present an updated overview of the effect of inflammation on the pharmacokinetic parameters of most of the drugs that are DMET substrates, for which therapeutic drug monitoring is recommended. Furthermore, we provide opinions on how to integrate the inflammatory status into pharmacogenetics, therapeutic drug monitoring, and population pharmacokinetic strategies to improve the personalization of drug treatment for each patient.

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“…One exception is that the half-life of fluoxetine was significantly reduced when peginterferon-α-2b was added, indicating an accelerated depletion of fluoxetine [ 32 ]. Another recent investigation also did not detect an influence of inflammation, as defined by CRP blood levels, on serum concentrations of citalopram or venlafaxine [ 33 ]. However, overall few studies have addressed the relationship of cytokines, antidepressants and drug metabolism, limiting the transferability of the aforementioned results in the context of affective disorders and antidepressant treatment.…”

Section: The Influence Of Cytokines On Pharma- Cokinetics and -Dynamimentioning

confidence: 99%

Inflammation and Immune Regulation as Potential Drug Targets in Antidepressant Treatment

Schmidt

Kirkby²,

Lichtblau³

2016

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Growing evidence supports a mutual relationship between inflammation and major depression. A variety of mechanisms are outlined, indicating how inflammation may be involved in the pathogenesis, course and treatment of major depression. In particular, this review addresses 1) inflammatory cytokines as markers of depression and potential predictors of treatment response, 2) findings that cytokines interact with antidepressants and non-pharmacological antidepressive therapies, such as electroconvulsive therapy, deep brain stimulation and physical activity, 3) the influence of cytokines on the cytochrome (CYP) p450-system and drug efflux transporters, and 4) how cascades of inflammation might serve as antidepressant drug targets. A number of clinical trials have focused on agents with immunmodulatory properties in the treatment of depression, of which this review covers nonsteroidal anti-inflammatory drugs (NSAIDs), cytokine inhibitors, ketamine, polyunsaturated fatty acids, statins and curcumin. A perspective is also provided on possible future immune targets for antidepressant therapy, such as toll-like receptor-inhibitors, glycogen synthase kinase-3 inhibitors, oleanolic acid analogs and minocycline. Concluding from the available data, markers of inflammation may become relevant factors for more personalised planning and prediction of response of antidepressant treatment strategies. Agents with anti-inflammatory properties have the potential to serve as clinically relevant antidepressants. Further studies are required to better define and identify subgroups of patients responsive to inflammatory agents as well as to define optimal time points for treatment onset and duration.

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Retrospective Pilot Study for Analysis of Antidepressant Serum Concentrations of Citalopram and Venlafaxine during Inflammation

Abstract: There was no major effect of inflammation on the metabolism of citalopram and venlafaxine. Because of the broad therapeutic indices of these 2 drugs, the drugs seem to be a good choice for the treatment of depression, even if an infection occurs.

Cited by 7 publications

References 24 publications

Impact of Acute Inflammation on Cytochromes P450 Activity Assessed by the Geneva Cocktail

Impact of Acute Inflammation on Cytochromes P450 Activity Assessed by the Geneva Cocktail

Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment

Inflammation and Immune Regulation as Potential Drug Targets in Antidepressant Treatment

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