LACK OF KINETIC INTERACTION BETWEEN ZOLPIDEM AND DULOXETINE: RESULTS FROM A DRUG-DRUG INTERACTION STUDY IN HEALTHY VOLUNTEERS

Ana-Maria  GHELDIU; Dana Maria  MUNTEAN; Maria Adriana  NEAG; Adina  POPA; Corina  BRICIU; Laurian  VLASE

doi:10.24193/subbchem.2019.3.13

LACK OF KINETIC INTERACTION BETWEEN ZOLPIDEM AND DULOXETINE: RESULTS FROM A DRUG-DRUG INTERACTION STUDY IN HEALTHY VOLUNTEERS

Authors

Ana-Maria GHELDIU Department of Pharmaceutical Botany, Faculty of Pharmacy, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. Email: anamaria.gheldiu@yahoo.com.
Dana Maria MUNTEAN Department of Pharmaceutical Technology and Biopharmaceutics, ‟Iuliu Hatieganu” University of Medicine and Pharmacy, Faculty of Pharmacy, Cluj-Napoca, Romania. Email: dana.muntean@umfcluj.ro. https://orcid.org/0000-0002-0200-1280
Maria Adriana NEAG Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, ‟Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania. Corresponding author: corina_briciu@yahoo.com. https://orcid.org/0000-0002-3904-2852
Adina POPA Department of Clinical Pharmacy, Faculty of Pharmacy, ‟Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania. Email: apopa@umfcluj.ro. https://orcid.org/0000-0002-4659-5500
Corina BRICIU Department of Clinical Pharmacy, Faculty of Pharmacy, ‟Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania. Email: corina_briciu@yahoo.com. https://orcid.org/0000-0003-2700-3589
Laurian VLASE Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Iuliu Hațieganu University of Medicine and Pharmacy; Department of Clinical Pharmacology and Pharmacokinetics. Email: laurian.vlase@umfcluj.ro. https://orcid.org/0000-0002-0664-3387

DOI:

https://doi.org/10.24193/subbchem.2019.3.13

Keywords:

zolpidem, duloxetine, kinetic interaction, healthy volunteers

Abstract

This open-label, non-randomized, two-period and sequential study aimed to evaluate a potential kinetic interaction between zolpidem ((N,N-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide), a widely known and used sedative-hypnotic and duloxetine ((3S)-N-methyl-3-naphthalen-1-yloxy-3-thiophen-2-ylpropan-1-amine), an antidepressant. A total of 23 healthy volunteers received the following medications: period 1 (Reference) - zolpidem 5 mg (single dose) and period 2 (Test) - zolpidem 5 mg and duloxetine 30 mg. Non-compartmental method was employed to determine the pharmacokinetic parameters of zolpidem and its main metabolite, zolpidem phenyl-4-carboxylic acid (Z4CA) while analysis of variance (ANOVA) was used to test the differences between study periods. Zolpidem exhibited similar pharmacokinetics with or without duloxetine (C_max: 59.64±27.64 ng/mL vs 53.28±22.77 ng/mL, AUC_0-t: 239.45±158.26 ng*h/mL vs 217.21±135.95 ng*h/mL, AUC_0-∞: 245.87±161.84 ng*h/mL vs 224.61±138.86 ng*h/mL, t_1/2: 2.97±2.06 vs 3.12±1.86 h). Subsequently, no marked changes were observed for Z4CA. The statistical test confirmed that duloxetine had no significant influence on the exposure to zolpidem and Z4CA (p<0.05 for all pharmacokinetic parameters). In conclusion, the study results excluded the possibility of a pharmacokinetic drug-drug interaction between these two drugs. Future investigations should focus on potential undesirable pharmacodynamic effects.

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STUDIA UBB CHEMIA, Volume 64 (LXIV), No. 3, September 2019

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Published

2019-09-30

How to Cite

GHELDIU, A.-M. ., MUNTEAN, D. M. ., NEAG, M. A. ., POPA, A. ., BRICIU, C. ., & VLASE, L. . (2019). LACK OF KINETIC INTERACTION BETWEEN ZOLPIDEM AND DULOXETINE: RESULTS FROM A DRUG-DRUG INTERACTION STUDY IN HEALTHY VOLUNTEERS. Studia Universitatis Babeș-Bolyai Chemia, 64(3), 153–162. https://doi.org/10.24193/subbchem.2019.3.13