Investigation of the Inhibitory Effect of Simvastatin on the Metabolism of Lidocaine Both in vitro and in vivo.
drug–drug interaction
in vitro model
lidocaine
pharmacokinetics
simvastatin
Journal
Drug design, development and therapy
ISSN: 1177-8881
Titre abrégé: Drug Des Devel Ther
Pays: New Zealand
ID NLM: 101475745
Informations de publication
Date de publication:
2020
2020
Historique:
received:
03
12
2019
accepted:
09
04
2020
entrez:
23
5
2020
pubmed:
23
5
2020
medline:
16
3
2021
Statut:
epublish
Résumé
Lidocaine has cardiovascular and neurologic toxicity, which is dose-dependent. Due to CYP3A4-involved metabolism, lidocaine may be prone to drug-drug interactions. Given statins have the possibility of combination with lidocaine in the clinic, we established in vitro models to assess the effect of statins on the metabolism of lidocaine. Further pharmacokinetic alterations of lidocaine and its main metabolite, monoethylglycinexylidide in rats influenced by simvastatin, were investigated. In vitro study revealed that simvastatin, among the statins, had the most significant inhibitory effect on lidocaine metabolism with IC Collectively, these results implied that simvastatin could evidently inhibit the metabolism of lidocaine both in vivo and in vitro. Accordingly, more attention and necessary therapeutic drug monitoring should be paid to patients with the concomitant coadministration of lidocaine and simvastatin so as to avoid unexpected toxicity.
Sections du résumé
BACKGROUND
BACKGROUND
Lidocaine has cardiovascular and neurologic toxicity, which is dose-dependent. Due to CYP3A4-involved metabolism, lidocaine may be prone to drug-drug interactions.
MATERIALS AND METHODS
METHODS
Given statins have the possibility of combination with lidocaine in the clinic, we established in vitro models to assess the effect of statins on the metabolism of lidocaine. Further pharmacokinetic alterations of lidocaine and its main metabolite, monoethylglycinexylidide in rats influenced by simvastatin, were investigated.
RESULTS
RESULTS
In vitro study revealed that simvastatin, among the statins, had the most significant inhibitory effect on lidocaine metabolism with IC
CONCLUSION
CONCLUSIONS
Collectively, these results implied that simvastatin could evidently inhibit the metabolism of lidocaine both in vivo and in vitro. Accordingly, more attention and necessary therapeutic drug monitoring should be paid to patients with the concomitant coadministration of lidocaine and simvastatin so as to avoid unexpected toxicity.
Identifiants
pubmed: 32440099
doi: 10.2147/DDDT.S241022
pii: 241022
pmc: PMC7212776
doi:
Substances chimiques
Anti-Arrhythmia Agents
0
Lidocaine
98PI200987
Simvastatin
AGG2FN16EV
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1739-1747Informations de copyright
© 2020 Wang et al.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest in this work.
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