PMID- 32588830
OWN - NLM
STAT- MEDLINE
DCOM- 20201030
LR  - 20201030
IS  - 2310-6972 (Print)
IS  - 2310-6905 (Linking)
VI  - 66
IP  - 3
DP  - 2020 May
TI  - [Modeling of drug-drug interactions between omeprazole and erythromycin with 
      cytochrome P450 3A4 in vitro assay].
PG  - 241-249
LID - 10.18097/PBMC20206603241 [doi]
AB  - In the present study the electrochemical system based on recombinant cytochrome 
      P450 3A4 (CYP3A4) was used for the investigation of potential drug-drug 
      interaction between medicinal preparations employed for Helicobacter pylori 
      eradication therapy. Drug interactions were demonstrated in association of 
      omeprazole as a proton pump inhibitor (PPI) and macrolide antibiotic erythromycin 
      during cytochrome P450 3A4-mediated metabolism. It was shown that in the presence 
      of omeprazole the rate of N-demethylase activity of CYP3A4 to erythromycin 
      measured by means of product (formaldehyde) formation decreased. 
      Mass-spectrometry analysis of omeprazole sulfone as a CYP3A4-mediated metabolite 
      demonstrated the absence of erythromycin influence on CYP3A4-dependent omeprazole 
      metabolism. This phenomenon may be explained by lower spectral dissociation 
      constant of CYP3A4-omeprazole complex (Kd = 18+/-2 muM) than that of 
      CYP3A4-erythromycin complex (Kd = 52 muM). Using the electrochemical model of 
      electrochemically-driven drug metabolism it is possible to register 
      CYP3A4-mediated catalytic conversion of certain drugs. In vitro experiments of 
      potential CYP3A4-mediated drug-drug interactions are in accordance with in silico 
      modeling with program PASS and PoSMNA descriptors in the case of 
      omeprazole/erythromycin combinations.
FAU - Koroleva, P I
AU  - Koroleva PI
AD  - Institute of Biomedical Chemistry, Moscow, Russia.
FAU - Kuzikov, A V
AU  - Kuzikov AV
AD  - Institute of Biomedical Chemistry, Moscow, Russia; Pirogov Russian National 
      Research Medical University (RNRMU), Moscow, Russia.
FAU - Masamrekh, R A
AU  - Masamrekh RA
AD  - Institute of Biomedical Chemistry, Moscow, Russia; Pirogov Russian National 
      Research Medical University (RNRMU), Moscow, Russia.
FAU - Filimonov, D A
AU  - Filimonov DA
AD  - Institute of Biomedical Chemistry, Moscow, Russia.
FAU - Dmitriev, A V
AU  - Dmitriev AV
AD  - Institute of Biomedical Chemistry, Moscow, Russia.
FAU - Zaviyalova, M G
AU  - Zaviyalova MG
AD  - Institute of Biomedical Chemistry, Moscow, Russia.
FAU - Rikova, S M
AU  - Rikova SM
AD  - Sechenov First Moscow Medical State University (Sechenov University), Moscow, 
      Russia.
FAU - Shich, E V
AU  - Shich EV
AD  - Sechenov First Moscow Medical State University (Sechenov University), Moscow, 
      Russia.
FAU - Makhova, A A
AU  - Makhova AA
AD  - Sechenov First Moscow Medical State University (Sechenov University), Moscow, 
      Russia.
FAU - Bulko, T V
AU  - Bulko TV
AD  - Institute of Biomedical Chemistry, Moscow, Russia.
FAU - Gilep, A A
AU  - Gilep AA
AD  - Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, 
      Minsk, Belarus.
FAU - Shumyantseva, V V
AU  - Shumyantseva VV
AD  - Institute of Biomedical Chemistry, Moscow, Russia; Pirogov Russian National 
      Research Medical University (RNRMU), Moscow, Russia.
LA  - rus
PT  - Journal Article
TT  - Modelirovanie mezhlekarstvennogo vzaimodeistviia omeprazola i eritromitsina s 
      ispol'zovaniem tsitokhrom R450-zavisimoi sistemy in vitro.
PL  - Russia (Federation)
TA  - Biomed Khim
JT  - Biomeditsinskaia khimiia
JID - 101196966
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Proton Pump Inhibitors)
RN  - 63937KV33D (Erythromycin)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - KG60484QX9 (Omeprazole)
SB  - IM
MH  - *Anti-Bacterial Agents/pharmacology
MH  - Cytochrome P-450 CYP3A
MH  - *Cytochrome P-450 Enzyme System
MH  - *Drug Interactions
MH  - *Erythromycin/pharmacology
MH  - *Omeprazole/pharmacology
MH  - *Proton Pump Inhibitors/pharmacology
OTO - NOTNLM
OT  - cytochrome P450 3A4
OT  - drug-drug interactions
OT  - electrochemical analysis
OT  - erythromycin
OT  - mass-spectrometry
OT  - omeprazole
EDAT- 2020/06/27 06:00
MHDA- 2020/10/31 06:00
CRDT- 2020/06/27 06:00
PHST- 2020/06/27 06:00 [entrez]
PHST- 2020/06/27 06:00 [pubmed]
PHST- 2020/10/31 06:00 [medline]
AID - 10.18097/PBMC20206603241 [doi]
PST - ppublish
SO  - Biomed Khim. 2020 May;66(3):241-249. doi: 10.18097/PBMC20206603241.