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

Abstract

Background/Aims: Attention deficit hyperactivity disorder (ADHD) is frequently associated with other psychiatric pathologies. Therefore, the present study investigated a possible pharmacokinetic interaction between atomoxetine (ATX), a treatment option for ADHD, and an antidepressant, namely, fluvoxamine (FVX). Methods: Designed as an open-label, non-randomized clinical trial, the study included 2 periods. In period 1 (reference), each subject received ATX 25 mg (single-dose), whereas in period 2 (test), all subjects were given a combination of ATX 25 mg + FVX 100 mg, following a 6-day pretreatment regimen with the enzymatic inhibitor. Non-compartmental methods were employed to determine the pharmacokinetic parameters of ATX and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide. Results: The results revealed significant differences between the study periods for C_max, AUC_0-t and AUC_0-_∞ values corresponding to ATX and its metabolite. Small, but statistically significant increases in AUC values were reported for both parent drug (1,583.05 ± 1,040.29 vs. 2,111.55 ± 1,411.59 ng*h/ml) and 4-hydroxyatomoxetine-O-glucuronide (5,754.71 ± 1,235.5 vs. 6,293.17 ± 1,219.34 ng*h/ml) after combined treatment of ATX and the enzymatic inhibitor. Conclusion: FVX had a modest effect on the pharmacokinetics of ATX and 4-hydroxyatomoxetine-O-glucuronide. The presence or absence of any clinical consequences associated with this pharmacokinetic drug-drug interaction needs to be established in future studies.

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

“…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].…”

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

“…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.…”

Influence of Fluvoxamine on Carvedilol’s Pharmacokinetics in Rats

“…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.…”