Evaluation of the Potential Pharmacokinetic Interaction between Atomoxetine and Fluvoxamine in Healthy Volunteers

Todor, Ioana; Popa, Adina; Neag, Maria Adriana; Bocşan, Ioana Corina; Buzoianu, Anca Dana; Vlase, Laurian; Gheldiu, Ana-Maria; Briciu, Corina

doi:10.1159/000452223

Cited by 7 publications

(3 citation statements)

References 14 publications

(15 reference statements)

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“…These data are consistent with other reports regarding the CYP2D6 inhibitory effect of sertraline, fluvoxamine and bupropion in vitro [27–29] and in vivo [13,30,31]. Recently, a study that describes the in vitro drug-drug interaction between carvedilol and citalopram was published [20].…”

Section: Discussionsupporting

confidence: 90%

Pharmacokinetic interactions study between carvedilol and some antidepressants in rat liver microsoms – a comparative study

Abrudan

Popa

Gheldiu

et al. 2019

Medicine and Pharmacy Reports

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Background and aims. Cardiovascular diseases and depressive disorders are some of the most frequent diseases. The probability of concomitant prescription of antihypertensive and antidepressive medication is increasing. The aim of this study was to investigate the enzyme inhibition by bupropion, sertraline and fluvoxamine on the metabolism of carvedilol using rat pooled liver microsomes and to assess the importance of these interactions from the pharmacokinetic mechanism point of view. Methods. Two substrate concentrations (0.5 and 1 μM) and four inhibitor concentrations (0, 0.1, 0.75 and 1.5 μM) were used for each tested inhibitor. Results. The results of the in vitro experiments showed a significant decrease of the metabolic rate of carvedilol to 4'-hydroxyphenyl carvedilol, for all tested inhibitors, when the inhibitor was added to the incubation mixture containing the substrate. Moreover, an increase of the area under the concentration-time curve for carvedilol was observed after incubation with each tested inhibitor compared with the control state (no inhibitor). The most potent inhibitor was sertraline, followed by fluvoxamine and bupropion. Conclusion. The co-administration of tested antidepressants led to a significant alteration of carvedilol’s metabolism in vitro. CYP2D6 inhibition is the main pharmacokinetic mechanism that can explain these drug-drug interactions, with possible clinical implications.

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Section: Discussionsupporting

confidence: 90%

Pharmacokinetic interactions study between carvedilol and some antidepressants in rat liver microsoms – a comparative study

Abrudan

Popa

Gheldiu

et al. 2019

Medicine and Pharmacy Reports

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“…Amiodarone is an inhibitor of CYP2D6 [25]. This family of enzymes is involved in the hepatic elimination of many beta blockers (metoprolol, carvedilol, nebivolol) [26,27]. As a consequence, it is possible to increase beta-blocker plasma concentrations and may need to decrease their dose in some situations.…”

Section: Discussionmentioning

confidence: 99%

Influence of concomitant medication on plasma concentration of amiodarone in patients with atrial fibrillation - A pilot study

Neag

Nacu

Cătinean

et al. 2019

Medicine and Pharmacy Reports

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Background. Although amiodarone is a drug with many side effects, it is one of the most commonly used drugs in the treatment and prophylaxis of supraventricular and ventricular arrhythmias. Aim. The purpose of this pilot study was to evaluate plasma concentrations of amiodarone in patients with atrial fibrillation (AF) and to identify possible drug-drug interactions between amiodarone and concomitant medications. Method. A prospective observational study was conducted in 27 consecutive patients treated with amiodarone from May to July 2017 in a Clinical University Hospital. The patients included met our inclusion criteria. HPLC-UV was the device used to determine the plasma concentration of amiodarone. Results. Only 51.8% of the patients had amiodarone plasma concentration within therapeutic interval (500-2500 ng/ml). The drugs associated to amiodarone in the therapeutic plan were diuretics, beta blockers, statins, antiplatelets, fluoroquinolones, non-steroidal anti-inflammatory drugs. We observed a statistically significant difference between the plasmatic concentrations of amiodarone in patients treated with furosemide vs. patients concomitantly treated with other drugs. Interactions between other mentioned drugs and amiodarone were not registered. We can report an underuse of amiodarone for more than 50% of the patients. Also, we found a significant interaction between furosemide and amiodarone, most likely through the interaction with MDR. Conclusion. Furosemide may influence the pharmacokinetics of P-gp-interfering drugs. However, the relevance of these findings needs to be confirmed and further research is needed to characterize the interaction between amiodarone and furosemide.

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“…It has a good absorption (more than 90%) and a low plasma protein binding (77%), being metabolized in the liver and excreted in urine [9,10,16]. Fluvoxamine is a potent inhibitor of CYP1A2 and CYP2C19 and moderate inhibitor of CYP2C9, CYP2D6 and CYP3A4 [4,32]. Due to fluvoxamine inhibitory effect on the enzymes which metabolize carvedilol, fluvoxamine may influence carvedilol's pharmacokinetics.…”

Section: Introductionmentioning

confidence: 99%

Influence of Fluvoxamine on Carvedilol’s Pharmacokinetics in Rats

Abrudan¹

2019

FARMACIA

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Carvedilol is one of the most used cardiovascular drugs, highly metabolized by CYP450 2D6, 1A2, 2C9. Fluvoxamine, an antidepressant agent, is a moderate/potent inhibitor of these enzymes. There is the risk of drug-drug interaction when these two drugs are concomitantly administered. The aim of this study was to investigate the drug-drug interactions between carvedilol and fluvoxamine in rats. There were two periods: reference and test. In the first period each rat received an oral dose of 3.57 mg/kg body weight carvedilol. In the test period, carvedilol was administered after a pre-treatment with multiple oral doses of fluvoxamine (14.28 mg/kg b.w.). HPLC-MS was used to determine the plasma concentration of carvedilol. The PK parameters were calculated by non-compartmental analysis. Fluvoxamine co-administered with carvedilol can change the PK parameters (increase AUC, t 1/2 , decrease the Cl). The present study demonstrated the pharmacokinetic drug-drug interaction between carvedilol and fluvoxamine in vivo. RezumatCarvedilolul este unul dintre cele mai utilizate medicamente cardiovasculare, intens metabolizat prin intermediul CYP450 2D6, 1A2, 2C9. Fluvoxamina, agent antidepresiv, este un inhibitor moderat/puternic al acestor enzime. La co-administrarea acestor două medicamente, există riscul apariției unei interacțiuni. Scopul studiului este de a investiga interacțiunea dintre carvedilol și fluvoxamină, la șobolani. Există două perioade: referință și test. În prima perioadă, fiecare șobolan a primit o doză de 3,57 mg/kg carvedilol. În perioada test, carvedilolul a fost administrat după un pre-tratament cu doze orale multiple de fluvoxamină (14.28 mg/kg). Pentru determinarea concentrațiilor plasmatice de carvedilol, s-a folosit sistemul HPLC-MS. Parametrii farmacocinetici s-au calculat prin analiza non-compartimentală. Co-administrarea fluvoxaminei cu carvedilolul a dus la modificarea parametrilor farmacocinetici (creșterea AUC, a t 1/2 , scăderea Cl). Studiul a demonstrat existența interacțiunii in vivo între carvedilol și fluvoxamină.

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Evaluation of the Potential Pharmacokinetic Interaction between Atomoxetine and Fluvoxamine in Healthy Volunteers

Cited by 7 publications

References 14 publications

Pharmacokinetic interactions study between carvedilol and some antidepressants in rat liver microsoms – a comparative study

Pharmacokinetic interactions study between carvedilol and some antidepressants in rat liver microsoms – a comparative study

Influence of concomitant medication on plasma concentration of amiodarone in patients with atrial fibrillation - A pilot study

Influence of Fluvoxamine on Carvedilol’s Pharmacokinetics in Rats

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