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. 2015;88(4):513-20.
doi: 10.15386/cjmed-488. Epub 2015 Nov 15.

The influence of paroxetine on the pharmacokinetics of atomoxetine and its main metabolite

Affiliations

The influence of paroxetine on the pharmacokinetics of atomoxetine and its main metabolite

Ioana Todor et al. Clujul Med. 2015.

Abstract

Background and aims: To evaluate the effects of paroxetine on the pharmacokinetics of atomoxetine and its main metabolite, 4-hydroxyatomoxetine-O-glucuronide, after coadministration of atomoxetine and paroxetine in healthy volunteers.

Methods: 22 healthy volunteers, extensive metabolizers, took part in this open-label, non-randomized, clinical trial. The study consisted of two periods: Reference, when a single oral dose of 25 mg atomoxetine was administrated to each subject and Test, when 25 mg atomoxetine and 20 mg paroxetine were coadministered. Between the two periods, the volunteers received an oral daily dose of 20-40 mg paroxetine, for 6 days. Atomoxetine and 4-hydroxyatomoxetine-O-glucuronide plasma concentrations were determined within the first 48 hours following drug administration. The pharmacokinetic parameters of both compounds were assessed using a non-compartmental method and the analysis of variance aimed at identifying any statistical significant differences between the pharmacokinetic parameters of atomoxetine and its main metabolite, corresponding to each study period.

Results: Paroxetine modified the pharmacokinetic parameters of atomoxetine. Cmax increased from 221.26±94.93 to 372.53±128.28 ng/mL, while AUC0-t and AUC0-∞ also increased from 1151.19±686.52 to 6452.37±3388.76 ng*h/mL, and from 1229.15±751.04 to 7111.74±4195.17 ng*h/mL respectively. The main metabolite pharmacokinetics was also influenced by paroxetine intake, namely Cmax, AUC0-t and AUC0-∞ decreased from 688.76±270.27 to 131.01±100.43 ng*h/mL, and from 4810.93±845.06 to 2606.04±923.88 and from 4928.55±853.25 to 3029.82 ±941.84 respectively.

Conclusions: Multiple-dose paroxetine intake significantly influenced atomoxetine and its active metabolite pharmacokinetics, causing a 5.8-fold increased exposure to atomoxetine and 1.6-fold reduced exposure to 4-hydroxyatomoxetine-O-glucuronide.

Keywords: 4-hydroxyatomoxetine; atomoxetine; drug interaction; paroxetine; pharmacokinetics.

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Figures

Figure 1
Figure 1
Mean (± SD) plasma levels of atomoxetine (ATM), after a single oral dose of atomoxetine 25 mg, before and after 6 days treatment with paroxetine (PXT) 20–40 mg/day, n=22. Insert: semilogarithmic presentation.
Figure 2
Figure 2
Mean (± SD) plasma levels of 4-hydroxyatomoxetine-O-glucuronide (AMM), after a single oral dose of atomoxetine 25 mg, before and after a 6 days treatment with paroxetine (PXT) 20–40 mg/day, n=22. Insert: semilogarithmic presentation.

References

    1. Aman MG, Smith T, Arnold LE, Corbett-Dick P, Tumuluru R, Hollway JA, et al. A review of atomoxetine effects in young people with developmental disabilities. Res Dev Disabil. 2014;35(6):1412–1424. - PMC - PubMed
    1. Antshel KM, Hargrave TM, Simonescu M, Kaul P, Hendricks K, Faraone SV. Advances in understanding and treating ADHD. BMC Med. 2011;9:72. - PMC - PubMed
    1. Ring BJ, Gillespie JS, Eckstein JA, Wrighton SA. Identification of the human cytochromes P450 responsible for atomoxetine metabolism. Drug Metab Dispos. 2002;30(3):319–323. - PubMed
    1. Sauer JM, Ponsler GD, Mattiuz EL, Long AJ, Witcher JW, Thomasson HR, et al. Disposition and metabolic fate of atomoxetine hydrochloride: the role of CYP2D6 in human disposition and metabolism. Drug Metab Dispos. 2003;31(1):98–107. - PubMed
    1. Simpson D, Plosker GL. Spotlight on atomoxetine in adults with attention-deficit hyperactivity disorder. CNS Drugs. 2004;18(6):397–401. - PubMed

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