Reversible and time-dependent inhibition of CYP3A4-mediated nifedipine oxidation by noscapine

Substrate-dependent inhibition of CYP3A4 might influence the extrapolation of drug interactions from the in vitro to in vivo situation. The aim of the present study is to investigate reversible and time-dependent inhibition of CYP3A4-mediated nifedipine oxidation by noscapine. Furthermore, in vitroi...

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Detalles Bibliográficos
Autores principales: Wang, Li-Ming, Yang, Ling, Li, Ming, Sun, De-Guang, Tang, Bo, Gao, Zhen-Ming, Liang, Rui, Qu, Yan-Qing, Fang, Zhong-Ze, Tang, Shu-Hong, Jin, Xue Li
Formato: Articulo Comunicacion
Lenguaje:Inglés
Publicado: 2011
Materias:
Farmacia
Warfarina
Sustratos
Noscapina
Nifedipino
Interacciones de Drogas
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/8385
http://www.latamjpharm.org/resumenes/30/9/LAJOP_30_9_2_2.pdf
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-8385
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Farmacia
Warfarina
Sustratos
Noscapina
Nifedipino
Interacciones de Drogas
spellingShingle Farmacia
Warfarina
Sustratos
Noscapina
Nifedipino
Interacciones de Drogas
Wang, Li-Ming
Yang, Ling
Li, Ming
Sun, De-Guang
Tang, Bo
Gao, Zhen-Ming
Liang, Rui
Qu, Yan-Qing
Fang, Zhong-Ze
Tang, Shu-Hong
Jin, Xue Li
Reversible and time-dependent inhibition of CYP3A4-mediated nifedipine oxidation by noscapine
topic_facet Farmacia
Warfarina
Sustratos
Noscapina
Nifedipino
Interacciones de Drogas
description Substrate-dependent inhibition of CYP3A4 might influence the extrapolation of drug interactions from the in vitro to in vivo situation. The aim of the present study is to investigate reversible and time-dependent inhibition of CYP3A4-mediated nifedipine oxidation by noscapine. Furthermore, in vitroin vivo extrapolation (IVIVE) was performed using in vitro parameters. The results showed that CYP3A4- mediated nifedipine oxidation activity was strongly inhibited with an IC<sub>50</sub> of 25.7 ± 5.4 μM. Kinetic analysis showed that inhibition of CYP3A4-mediated nifedipine oxidation by noscapine was best fit to a noncompetitive manner with Ki value of 10.9 μM. IC50 shift experiment showed that IC50 was significantly decreased from 25.7 ± 5.4 μM to 0.34 ± 0.07 μM after pre-incubation with noscapine for 30 min, which indicated that time-dependent inhibition existed for inhibition of CYP3A4 by noscapine. The AUC of (R)- warfarin was predicted to increase by 0.5 % using C<sub>max</sub> or 0.2 % using unbound C<sub>max</sub> with reversible inhibition prediction equation, while the AUC of (R)-warfarin was estimated to increase by 23.1 % using C<sub>max</sub> or 10.4 % using unbound C<sub>max</sub> with TDI prediction equation. Inhibition of CYP3A4 by noscapine showed substrate-dependent inhibition behaviour. However, the results obtained from IVIVE are very similar using testosterone or nifedipine as probe substrates.
format Articulo
Comunicacion
author Wang, Li-Ming
Yang, Ling
Li, Ming
Sun, De-Guang
Tang, Bo
Gao, Zhen-Ming
Liang, Rui
Qu, Yan-Qing
Fang, Zhong-Ze
Tang, Shu-Hong
Jin, Xue Li
author_facet Wang, Li-Ming
Yang, Ling
Li, Ming
Sun, De-Guang
Tang, Bo
Gao, Zhen-Ming
Liang, Rui
Qu, Yan-Qing
Fang, Zhong-Ze
Tang, Shu-Hong
Jin, Xue Li
author_sort Wang, Li-Ming
title Reversible and time-dependent inhibition of CYP3A4-mediated nifedipine oxidation by noscapine
title_short Reversible and time-dependent inhibition of CYP3A4-mediated nifedipine oxidation by noscapine
title_full Reversible and time-dependent inhibition of CYP3A4-mediated nifedipine oxidation by noscapine
title_fullStr Reversible and time-dependent inhibition of CYP3A4-mediated nifedipine oxidation by noscapine
title_full_unstemmed Reversible and time-dependent inhibition of CYP3A4-mediated nifedipine oxidation by noscapine
title_sort reversible and time-dependent inhibition of cyp3a4-mediated nifedipine oxidation by noscapine
publishDate 2011
url http://sedici.unlp.edu.ar/handle/10915/8385
http://www.latamjpharm.org/resumenes/30/9/LAJOP_30_9_2_2.pdf
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