Effect of Fluvoxamine on the Pharmacokinetics of Imipramine and Desipramine in Healthy Subjects

Spina, Edoardo; Pollicino, A; Avenoso, Angela; Campo, Giuseppe M.; Perucca, Emilio; Caputi, Achille P.

doi:10.1097/00007691-199306000-00011

Cited by 132 publications

(43 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After evaluating the magnitude of all the aforementioned metabolism-mediated pharmacokinetic interactions involving nebivolol and antidepressants, fluvoxamine had a much smaller influence upon nebivolol pharmacokinetics compared to other antidepressants like bupropion, paroxetine or fluoxetine. Until now, very few studies have investigated the potential pharmacokinetic interaction between fluvoxamine and CYP2D6 substrates, all of which have revealed that this enzymatic inhibitor produced only small changes in the pharmacokinetics of desipramine, dextrometorphan or risperidone (31)(32)(33). The present study results also confirmed this hypothesis that only a modest impact on nebivolol exposure can be noticed after its association with fluvoxamine.…”

Section: Discussionsupporting

confidence: 86%

Investigation of a Potential Pharmacokinetic Interaction Between Nebivolol and Fluvoxamine in Healthy Volunteers

et al. 2017

View full text Add to dashboard Cite

-PURPOSE:To investigate whether fluvoxamine coadministration can influence the pharmacokinetic properties of nebivolol and its active hydroxylated metabolite (4-OH-nebivolol) and to assess the consequences of this potential pharmacokinetic interaction upon nebivolol pharmacodynamics. METHODS:This open-label, non-randomized, sequential clinical trial consisted of two periods: Period 1 (Reference), during which each volunteer received a single dose of 5 mg nebivolol and Period 2 (Test), when a combination of 5 mg nebivolol and 100 mg fluvoxamine was given to all subjects, after a 6-days pretreatment regimen with fluvoxamine (50-100 mg/day). Non-compartmental analysis was used to determine the pharmacokinetic parameters of nebivolol and its active metabolite. The pharmacodynamic parameters (blood pressure and heart rate) were assessed at rest after each nebivolol intake, during both study periods. RESULTS: Fluvoxamine pretreatment increased C max and AUC 0-∞ of nebivolol (C max : 1.67 ± 0.690 vs 2.20 ± 0.970 ng/mL; AUC 0-∞ : 12.1 ± 11.0 vs 19.3 ± 19.5 ng*h/mL ) and of its active metabolite (C max : 0.680 ± 0.220 vs 0.960 ± 0.290 ng/mL; AUC 0-∞ : 17.6 ±20.1 vs 25.5 ± 29.9 ng*h/mL). Apart from C max , AUC 0-t and AUC 0-∞ , the other pharmacokinetic parameters (t max , k el and t ½ ) were not significantly different between study periods. As for the pharmacodynamic analysis, decreases in blood pressure and heart rate after nebivolol administration were similar with and without fluvoxamine concomitant intake. CONCLUSIONS: Due to enzymatic inhibition, fluvoxamine increases the exposure to nebivolol and its active hydroxylated metabolite in healthy volunteers. This did not influence the blood pressure and heart-rate lowering effects of the beta-blocker administered as single-dose. However, more detail studies involving actual patients are required to further investigate the clinical relevance of this drug interaction.

show abstract

Section: Discussionsupporting

confidence: 86%

Investigation of a Potential Pharmacokinetic Interaction Between Nebivolol and Fluvoxamine in Healthy Volunteers

et al. 2017

View full text Add to dashboard Cite

show abstract

“…This mechanism is the source of the pharmacokinetic interaction between fluvoxamine and theophylline as well as other drugs, such as clozapine [40,42], propranolol [48] and imipramine [49,50]. Our data also illustrate that fluvoxamine could be an important probe for the assessment of the role of CYP1A2 in the metabolism of drugs and other xenobiotics in humans, in addition to furafylline [51,52].…”

Section: Discussionmentioning

confidence: 71%

Selective serotonin reuptake inhibitors and theophylline metabolism in human liver microsomes: potent inhibition by fluvoxamine.

Rasmussen¹,

Mäenpää²,

Pelkonen³

et al. 1995

Brit J Clinical Pharma

141

View full text Add to dashboard Cite

1 Fluvoxamine and seven other selective serotonin reuptake inhibitors (SRRI) were tested for their ability to inhibit a number of human cytochrome P450 isoforms (CYPs). 2 None of the drugs showed potent inhibition of CYP2A6 (coumarin 7-hydroxylase) or CYP2E1 (chlorzoxazone 6-hydroxylase), while norfluoxetine was the only 5 Ethanol inhibited the formation of 1,3-dimethyluric acid with a Ki value of 300 JM, a value which is consistent with inhibition of CYP2E1. Ethanol and fluvoxamine both inhibited 8-hydroxylation by about 45% and, in combination, the compounds decreased the formation of 1,3-dimethyluric acid by 90%, indicating that CYP1A2 and CYP2E1 are equally important isoforms for the 8-hydroxylation of theophylline. 6 It is concluded that pharmacokinetic interaction between fluvoxamine and theophylline is due to potent inhibition of CYP1A2.

show abstract

“…A similar interaction between tricyclic antidepressants and fluvoxamine has been demonstrated [9,10]. Spina et al [11] showed that fluvoxamine markedly inhibited the N-demethylation of imipramine without affecting the CYP2D6 mediated hydroxylation of desipramine [12]. Br0sen et al [13] have shown in vitro that fluvoxamine is a potent inhibitor of phenacetin O-deethylation, a reaction catalysed by CYP1A2.…”

Section: Introductionmentioning

confidence: 72%

Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test.

Bertilsson

Carrillo

et al. 1994

Brit J Clinical Pharma

266

116

View full text Add to dashboard Cite

In a previous study we showed that the disposition of clozapine after a single oral dose is unrelated to either debrisoquine or S-mephenytoin hydroxylation polymorphism. The same 14 healthy subjects studied in that investigation were given 150 mg of caffeine. The reciprocal of plasma clozapine AUC (0,24), was correlated with an index of the N3-demethylation of caffeine (r, = 0.84; P = 0.0024), used as a measure of cytochrome P4501A2 (CYP1A2) activity. Ni-and N7-demethylation indices of caffeine also reflect CYP1A2 activity and were also correlated with clozapine clearance (rs = 0.89 and 0.85; P = 0.0013 and 0.0023; respectively). No significant relationships with xanthine oxidase and N-acetyl transferase activity, also assessed by a caffeine test, were found. This study suggests that clozapine is metabolised by CYP1A2 to a major extent.

show abstract

Effect of Fluvoxamine on the Pharmacokinetics of Imipramine and Desipramine in Healthy Subjects

Cited by 132 publications

References 0 publications

Investigation of a Potential Pharmacokinetic Interaction Between Nebivolol and Fluvoxamine in Healthy Volunteers

Investigation of a Potential Pharmacokinetic Interaction Between Nebivolol and Fluvoxamine in Healthy Volunteers

Selective serotonin reuptake inhibitors and theophylline metabolism in human liver microsomes: potent inhibition by fluvoxamine.

Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test.

Contact Info

Product

Resources

About