Drug Design, Development and Therapy (May 2020)

Investigation of the Inhibitory Effect of Simvastatin on the Metabolism of Lidocaine Both in vitro and in vivo

  • Wang Y,
  • Ou-yang Q,
  • Huang W,
  • Huang H,
  • Zhuang X,
  • Lin Q,
  • Zeng D

Journal volume & issue
Vol. Volume 14
pp. 1739 – 1747

Abstract

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Ying Wang,1 Qiu-geng Ou-yang,2 Wan-li Huang,3 Huan-le Huang,2,4 Xin-lei Zhuang,1 Qian-meng Lin,2 Da-li Zeng4 1Pharmacy Department, Ningbo Medical Center Lihuili Hospital, Ningbo 315000, Zhejiang Province, People’s Republic of China; 2School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, People’s Republic of China; 3School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province,People’s Republic of China; 4Department of Pharmacy, Ruian Hospital of Traditional Chinese Medicine, Wenzhou 325000, Zhejiang Province, People’s Republic of ChinaCorrespondence: Da-li ZengDepartment of Pharmacy, Ruian Hospital of Traditional Chinese Medicine, Anyang Road, Ruian City, Wenzhou, Zhejiang Province Email [email protected]: 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: 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: In vitro study revealed that simvastatin, among the statins, had the most significant inhibitory effect on lidocaine metabolism with IC50 of 39.31 μM, 50 μM and 15.77 μM for RLM, HLM and CYP3A4.1, respectively. Consistent with in vitro results, lidocaine concomitantly used with simvastatin in rats was associated with 1.2-fold AUC(0-t), 1.2-fold AUC(0-∞), and 20%-decreased clearance for lidocaine, and 1.4-fold Cmax for MEGX compared with lidocaine alone.Conclusion: 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.Keywords: lidocaine, simvastatin, drug–drug interaction, pharmacokinetics, in vitro model

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