Tofisopam hatása a humán rekombináns CYP3A4 szuperszóma enzim aktivitására

Translated title of the contribution: Effect of tofisopam on CYP3A4 enzyme activity on human recombinant 3A4 supersome

Mária Tóth, Judit Bajnógel, András Egyed, Sándor Drabant, Judit Tömlo, Imre Klebovich

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Tofisopam is an anxiolytic agent of the BZD group, chemically 1(3-4 dimethoxyphenyl)-4methyl-5-ethyl-7,8 dimethoxy-5H-2,3-benzodiazepine. TZP differs from the traditional 1,4-benzodiazepines regarding the positions of the nitrogen atoms. Three clinical cases were reported where tofisopam increased the blood level of immunosuppressive agent leading clinically relevant adverse drug reaction and necessitating reduction of the dose of the drugs or discontinuation of the administration of tofisopam. The administered immunosuppressive agent is a substrate of the CYP3A4 system, so the effect of tofisopam on the CYP3A4 enzyme was investigated in vitro using human recombinant CYP3A4 supersome. Benzyoxy-4-(trifluoromethyl)-coumarin (BFC) was used as substrate. Tofisopam in 0.1, 0.25, 0.5, 0.75, 1 and 5 μmol/l concentrations inhibited dose dependently the enzyme activity. Activity inhibition rates were 4%, 29%, 40%, 56%, 61% and 94%, respectively and the IC50 was 0.8 μmol/l. The IC50 of positive control substance ketoconazole was 0.03 μmol/l. In in vitro experiments the inhibitory effect of tofisopam was lower than that of ketoconazole (potent CYP3A4 inhibitor) with an order of magnitude. According to the in vitro results it could be concluded that tofisopam is an inhibitor of CYP3A4 but to clarify the clinical importance of this inhibition further human clinical data are needed.

Translated title of the contributionEffect of tofisopam on CYP3A4 enzyme activity on human recombinant 3A4 supersome
Original languageHungarian
Pages (from-to)195-198
Number of pages4
JournalActa pharmaceutica Hungarica
Volume75
Issue number4
Publication statusPublished - Dec 1 2005

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Tóth, M., Bajnógel, J., Egyed, A., Drabant, S., Tömlo, J., & Klebovich, I. (2005). Tofisopam hatása a humán rekombináns CYP3A4 szuperszóma enzim aktivitására. Acta pharmaceutica Hungarica, 75(4), 195-198.