Influence of Coadministration of Fluoxetine on Cisapride Pharmacokinetics and QTc Intervals in Healthy Volunteers

Zhao, Qinying; Wojcik, Mary Ann; Parier, Jean-Loup; Pesco-Koplowitz, Luana

doi:10.1592/phco.21.2.149.34109

Cited by 20 publications

(7 citation statements)

References 20 publications

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“…In current study violacein and azole combination recorded activity at very low concentration than the individual compounds. The benefits of using synergistic drug combination include a wider spectrum of efficiency, improved safety and tolerability and an enhanced reduction of antifungal resistance (Lewis and Kontoyiannis, 2001 ; Endo et al, 2010 ). In our study, we investigated the synergistic effect of violacein and four clinically used azole drugs (ketoconazole, fluconazole, itraconazole, and clotrimazole).…”

Section: Discussionmentioning

confidence: 99%

Synergistic combination of violacein and azoles that leads to enhanced killing of major human pathogenic dermatophytic fungi Trichophyton rubrum

Anju

Kumar

Krishnakumar

et al. 2015

Front. Cell. Infect. Microbiol.

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Superficial mycoses caused by dermatophytic fungi such as Trichophyton rubrum represent the most common type of worldwide human infection affecting various keratinized tissues in our body such as the skin, hair, and nails, etc. The dermatophytic infection is a significant public health threat due to its persistent nature and high recurrence rates, and thus alternative treatments to cure this fungal infection are urgently required. The present study mainly focused on the synergistic activity of violacein with four azole drugs (ketoconazole, fluconazole, clotrimazole, and itraconazole) against T. rubrum. The synergistic antifungal activities of violacein and azoles were measured by checkerboard microdilution and time-kill assays. In our study, combinations of violacein and azoles predominantly recorded synergistic effect (FIC index < 0.5). Significant synergistic value was recorded by the combination of violacein and clotrimazole. Time-kill assay by the combination of MIC concentration of violacein and azoles recorded that the growth of the T. rubrum was significantly arrested after 4–12 h of treatment. The combination of violacein and azoles leads to the enhanced inhibition of mycelial growth and conidial germination. Moreover combination enhanced the rate of release of intracellular materials. Morphological changes by SEM analysis were also prominent with the combination. A normal human cell line [Foreskin (FS) normal fibroblast] was used to check the cytotoxicity of violacein. Interestingly violacein recorded no cytotoxicity up to 100 μg/ml. The in vitro synergistic effect of violacein and azoles against clinically relevant fungi, T. rubrum, is reported here for the first time. Finally, our findings support the potential use of the violacein as an antifungal agent especially against dermatophytic fungi T. rubrum.

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Section: Discussionmentioning

confidence: 99%

Synergistic combination of violacein and azoles that leads to enhanced killing of major human pathogenic dermatophytic fungi Trichophyton rubrum

Anju

Kumar

Krishnakumar

et al. 2015

Front. Cell. Infect. Microbiol.

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“…As depression and gastroesophageal reflux disease often occur together and many of SSRI (selective serotonin reuptake inhibitors) demonstrate some extent of CYP inhibitory properties, it is important to determine whether potentially harmful interactions occur between antidepressants and cisapride. In the two identified studies fluoxetine [ 95 ] and sertraline [ 96 ] were studied for effects of their interaction with cisapride. Data from both studies indicate that cisapride can be safely administered to patients who are treated with fluoxetine and sertraline while neither fluoxetine nor cisapride, nor sertraline, nor their combination induced statistically or clinically significant ECG parameters change.…”

Section: Resultsmentioning

confidence: 99%

Drug-drug interactions and QT prolongation as a commonly assessed cardiac effect - comprehensive overview of clinical trials

Wiśniowska

Tylutki

Wyszogrodzka

et al. 2016

BMC Pharmacol Toxicol

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Background: Proarrhythmia assessment is one of the major concerns for regulatory bodies and pharmaceutical industry. ICH guidelines recommending preclinical tests have been established in attempt to eliminate the risk of drug-induced arrhythmias. However, in the clinic, arrhythmia occurrence is determined not only by the inherent property of a drug to block ion currents and disturb electrophysiological activity of cardiac myocytes, but also by many other factors modifying individual risk of QT prolongation and subsequent proarrhythmia propensity. One of those is drug-drug interactions. Since polypharmacy is a common practice in clinical settings, it can be anticipated that there is a relatively high risk that the patient will receive at least two drugs mutually modifying their proarrhythmic potential and resulting either in triggering the occurrence or mitigating the clinical symptoms. The mechanism can be observed either directly at the pharmacodynamic level by competing for the molecular targets, or indirectly by modifying the physiological parameters, or at the pharmacokinetic level by alteration of the active concentration of the victim drug. Methods: This publication provides an overview of published clinical studies on pharmacokinetic and/or pharmacodynamic drug-drug interactions in humans and their electrophysiological consequences (QT interval modification). Databases of PubMed and Scopus were searched and combinations of the following keywords were used for Title, Abstract and Keywords fields: interaction, coadministration, combination, DDI and electrocardiographic, QTc interval, ECG. Only human studies were included. Over 4500 publications were retrieved and underwent preliminary assessment to identify papers accordant with the topic of this review. 76 papers reporting results for 96 drug combinations were found and analyzed.

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“…We, therefore, compared our hERG inhibition data obtained in serum to published clinical data that concurrently measured QT interval prolongation and total plasma levels of these drugs. For cisapride, total plasma levels ranging from approximately 100 to 300 nM have been shown to produce QT interval prolongation ranging from 5 to 38 ms (van Haarst et al ., ; Zhao et al ., ; Cools et al ., ). These plasma levels correspond to approximately 5–15% inhibition of hERG by cisapride in pure serum and are in the range of the calculated IC 10 value which measured 182 nM.…”

Section: Discussionmentioning

confidence: 99%

Observations on conducting whole‐cell patch clamping of the hERG cardiac K⁺ channel in pure human serum

Kang

Luo

Searles

et al. 2016

J of Applied Toxicology

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Inhibition of the human ether-a-go-go-related gene (hERG) K channel by drugs leads to QT prolongation on the electrocardiogram and can result in serious cardiac arrhythmia. For this reason, screening of drugs on hERG is mandatory during the drug development process. Patch clamp electrophysiology in a defined physiological saline solution (PSS) represents the standard method for assaying drug effects on the channel. To make the assay more translatable to clinical studies, we have conducted whole-cell patch clamping of hERG using pure human serum as the extracellular medium. Pure human serum had little effect on the hERG channel waveform or the current-voltage relationship when compared to PSS. hERG current recordings were highly stable in serum at room temperature, but prolonged recordings at the physiological temperature required prior heat inactivation of the serum. Compared to PSS, the IC values, conducted at room temperature, of the classic hERG blocking drugs cisapride, moxifloxacin, and terfenadine were shifted to the right by an extent predicted by their known plasma protein binding, but we did not detect any differences in IC s between male and female serum. Total plasma levels of these drugs associated with clinical QT prolongation corresponded to small (<15%) inhibition of hERG current in pure serum suggesting that minor inhibition of the channel leads to observable pharmacodynamic effects. Conducting whole-cell patch clamping of hERG in human serum has the potential to make the assay more translatable to clinical studies and improve its predictive value for safety testing. Copyright © 2016 John Wiley & Sons, Ltd.

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Influence of Coadministration of Fluoxetine on Cisapride Pharmacokinetics and QTc Intervals in Healthy Volunteers

Abstract: Cisapride can be administered safely to patients receiving low therapeutic dosages of fluoxetine.

Cited by 20 publications

References 20 publications

Synergistic combination of violacein and azoles that leads to enhanced killing of major human pathogenic dermatophytic fungi Trichophyton rubrum

Synergistic combination of violacein and azoles that leads to enhanced killing of major human pathogenic dermatophytic fungi Trichophyton rubrum

Drug-drug interactions and QT prolongation as a commonly assessed cardiac effect - comprehensive overview of clinical trials

Observations on conducting whole‐cell patch clamping of the hERG cardiac K⁺ channel in pure human serum

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Influence of Coadministration of Fluoxetine on Cisapride Pharmacokinetics and QTc Intervals in Healthy Volunteers

Abstract: Cisapride can be administered safely to patients receiving low therapeutic dosages of fluoxetine.

Cited by 20 publications

References 20 publications

Synergistic combination of violacein and azoles that leads to enhanced killing of major human pathogenic dermatophytic fungi Trichophyton rubrum

Synergistic combination of violacein and azoles that leads to enhanced killing of major human pathogenic dermatophytic fungi Trichophyton rubrum

Drug-drug interactions and QT prolongation as a commonly assessed cardiac effect - comprehensive overview of clinical trials

Observations on conducting whole‐cell patch clamping of the hERG cardiac K+ channel in pure human serum

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Observations on conducting whole‐cell patch clamping of the hERG cardiac K⁺ channel in pure human serum