Fluvoxamine maleate; Disposition in man

Bree, H. de; Schoot, J. B. van der; Post, L. C.

doi:10.1007/bf03188743

Cited by 44 publications

(14 citation statements)

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“…The gastrointestinal absorption of uvoxamine is almost complete [2], and the oral bioavailability has been found to be 40±60% after single-dose administration [3]. Fluvoxamine is extensively metabolized in the liver, and less than 4% is excreted unmetabolized [2]. Eleven metabolites have been found in urine, and nine of these have been identi®ed [4].…”

Section: Introductionmentioning

confidence: 97%

“…The original drug substance is virtually entirely in the E con®guration [1]. The gastrointestinal absorption of uvoxamine is almost complete [2], and the oral bioavailability has been found to be 40±60% after single-dose administration [3]. Fluvoxamine is extensively metabolized in the liver, and less than 4% is excreted unmetabolized [2].…”

Section: Introductionmentioning

confidence: 98%

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The major fluvoxamine metabolite in urine is formed by CYP2D6

Spigset¹,

Axelsson²,

Norström³

et al. 2001

Eur J Clin Pharmacol

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Objective: Previous studies have shown that uvoxamine is metabolized by CYP1A2 and CYP2D6, but there is no information on the impact the various CYP enzymes have on the dierent metabolic pathways of¯uvoxamine biotransformation. The present study was designed to investigate this issue. Methods: The major¯uvoxamine metabolite, the 5-demethoxylated carboxylic acid metabolite, was analyzed in urine from 50 healthy volunteers after intake of a single oral dose of 50 mg¯uvoxamine, and the formation clearance for the metabolite (CL m ) was calculated. Of the subjects, 28 were non-smoking CYP2D6 and CYP2C19 extensive metabolizers (EMs), 12 were smokers and were thus considered to have an induced CYP1A2 activity, 5 were CYP2D6 poor metabolizers (PMs), and 5 were CYP2C19 PMs. In 11 of the nonsmoking EMs, 200 mg caeine was given at another occasion in order to calculate oral caeine clearance as a measure of CYP1A2 activity. In addition, CL m was calculated in ten other subjects given increasing doses of uvoxamine for 4 weeks. Results: Oral clearance of¯uvoxamine was signi®cantly higher in smokers, and signi®cantly lower in CYP2D6 PMs than in non-smoking EMs. CL m was 78% lower in CYP2D6 PMs than in the EMs. Smoking and being a CYP2C19 PM did not in¯uence CL m . There was no signi®cant correlation between oral caeine clearance and CL m . CL m decreased with increasing¯uvoxamine dosage, but the decrease in oral clearance was even higher. Conclusion:These results indicate that CYP2D6 catalyzes the major metabolic pathway of¯uvoxamine, whereas CYP1A2 seems to catalyze other less important pathways. Both the CYP2D6 and the CYP1A2 pathways seem to be saturated in parallel with increasinḡ uvoxamine dosage.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

The major fluvoxamine metabolite in urine is formed by CYP2D6

Spigset¹,

Axelsson²,

Norström³

et al. 2001

Eur J Clin Pharmacol

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“…A pharmacokinetic study showed that fluvoxamine was well absorbed after oral administration (Benfield and Ward, 1986). Peak plasma concentrations, occurring 1.5 to 8 h after oral administration of 100 mg of fluvoxa- mine, ranged from 31 to 87pglL (De Bree, et al, 1983). The volume of distribution was over 5 L/kg, and protein binding was about 77%.…”

Section: Introductionmentioning

confidence: 98%

“…Fluvoxamine is an investigational serotonin reuptake inhibitor(SR1) (Benfield, 1986;Claassen, 1977;De Bree et al, 1983;Goodman et al, 1989Goodman et al, ,1990Lapierre e t a f . , 1983Lapierre e t a f .…”

Section: Introductionmentioning

confidence: 98%

Determination of fluvoxamine concentration in plasma by reversed‐phase liquid chromatography

Wong

Kranzler

Dellafera

et al. 1994

Biomedical Chromatography

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Fluvoxamine, a serotonin re-uptake inhibitor, was quantified in plasma by modifying a previously published procedure for monitoring plasma concentrations of tricyclic antidepressants. Alkalinized plasma samples were extracted with n-hexane/isoamyl alcohol, followed by back-extraction with diluted phosphoric acid. The extracts were analysed by reversed-phase liquid chromatography using a C-18 column, with phosphate/acetonitrile as the mobile phase. The assay was linear from 10 to 800 micrograms/L. Precision studies showed within-run and day-to-day coefficients of variation to be 4.5 and 6.8%, respectively. Desipramine interfered with the detection of fluvoxamine. The assay was used to measure a total of 8 plasma samples from 4 alcohol-dependent patients medicated with fluvoxamine as an adjunct to relapse prevention psychotherapy. In these patients, the plasma concentrations ranged from 54 to 241 micrograms/L. Dosage of fluvoxamine, duration of treatment, interval between last dosage and blood collection were associated with effects on plasma concentrations that were consistent with the pharmacokinetic profile of fluvoxamine.

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“…After oral administration, fluvoxamine reaches its maximum plasma concentration after 5-6 hours, and its volume of distribution is extensive (25 liters/kg). It has an elimination half-life of approximately 15 hours and reaches steady state in plasma after about 10 days (16)(17)(18)(19). Fluvoxamine displays nonlinear steady-state pharmacokinetics in plasma, with levels 30% to 50% higher than predicted from single-dose data (20).…”

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confidence: 99%