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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

(English title: Physiological Journal)

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2025; 71(3): 81-88

Interaction of propoxazepam with human liver cytochrome P450 2C9 and its therapeutic implications

M.Ya. Golovenko1, I. P. Valivodz1, A.S. Reder2, V .B. Larionov1, V .E. Litvinova3

  1. A.V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences of Ukraine; Odesa, Ukraine
  2. SLC «INTERCHEM», Odesa, Ukraine
  3. Odesa National University, Faculty of Chemistry and Pharmacy, Ukraine
DOI: https://doi.org/10.15407/fz71.03.081


Abstract

Propoxazepam is a novel benzodiazepine-derived analgesic that has completed Phase I clinical trials, dem- onstrating its safety and appropriate pharmacokinetics. Phase II trials are currently underway to evaluate its effectiveness in treating neuropathic pain. This study aimed to investigate the effect of propoxazepam on CYP2C9 activity in human liver microsomes and to determine the inhibitory mechanisms underlying its action on the enzyme. These findings may contribute to a comprehensive assessment of potential drug-drug interactions involving propoxazepam. To evaluate CYP2C9 activity, we used the reaction of diclofenac hydroxylation and selective inhibitors (as positive controls): sulfaphenazole for reversible and thienylic acid for metabolism-dependent inhibition. Propoxazepam inhibited CYP2C9 activity, with IC 50 values of 32.7 ± 2.8 μmol/l for reversible and 49.0 ± 12.6 μmol/l for metabolism-dependent inhibition. The highest concentration of free, unbound propoxazepam in plasma that could result in interaction is ≥0.327 µmol/l (0.133 µg/ml). This corresponds, given that only 1.96% of total plasma propoxazepam exists in the free fraction, to a total plasma concentration of 6.8 µg/ml, but the concentrations in the volunteer`s blood are much lower after single oral administration.

Keywords: propoxazpepam; CYP2C9; diclofenac; sulphaphenazole; tienilic acid; revercible inhibition; metabolism dependent inhibition; drug-drug interaction

Full text: (PDF, in English)

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