Effects of CYP2D6 and CYP2C19 genetic polymorphisms and cigarette smoking on the pharmacokinetics of tolperisone

Byeon, Ji-Young; Cho, Chang‑Keun; Kang, Pureum; Kim, Se-Hyung; Jang, Choon-Gon; Lee, Seok-Yong; Lee, Yun Jeong

doi:10.1007/s12272-023-01462-1

Cited by 4 publications

(1 citation statement)

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“…Genetic polymorphisms of CYP2D6 and CYP2C19 and cigarette smoking independently and significantly affected tolperisone pharmacokinetics, and these factors together may have a greater effect (eg, non-smoking patients with the CYP2D6*10/*10 and CYP2C19 PM genotype had a 25.9-fold increase in AUC compared to smokers with the CYP2D6*wt/*wt and CYP2C19 EM genotype). 70 A two-fold increase in oral baclofen clearance was associated with the single-nucleotide polymorphism of ABCC9 ( rs11046232 , heterozygous AT versus TT genotype). 71 Smoking can reduce plasma concentrations and the effects of tizanidine.…”

Section: Discussionmentioning

confidence: 99%

Tizanidine: Advances in Pharmacology & Therapeutics and Drug Formulations

Zhu,

Wang,

Zhou

2024

JPR

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Background Skeletal muscle relaxants (SMRs) are widely used in treating musculoskeletal conditions. All SMRs, with the exception of baclofen and tizanidine, are on the list of 2023 American Geriatrics Society Beers Criteria ® for potentially inappropriate medication use in older adults. In our geriatric practice, off-label use of tizanidine as preemptive analgesia drove us to find recent advances in its pharmacology and therapeutics. An update review of tizanidine was thus presented, aiming to bring the latest knowledge to clinicians and promote further research and practical exploration. Methods Relevant literature up to December 2023 was identified through searches of PubMed, Web of Science, and Embase. Results Tizanidine, a centrally acting alpha-2 adrenoceptor agonist with both antispastic and antispasmodic activity, shows efficacy in the common indications for all SMRs. From the perspective of drug safety, tizanidine has lower incidences of adverse events (injury, delirium, encephalopathy, falls, and opioid overdose) compared to baclofen, no association with risk of Alzheimer’s disease as with orphenadrine, no risk of serotonin syndrome like metaxalone when comedicated with serotonergic drugs, no significant pharmacokinetic changes in CYP2C19 poor metabolizers unlike diazepam and carisoprodol, and no physically addictive or abuse properties like carisoprodol and diazepam. From the perspective of new and potential therapeutic uses, tizanidine has additional benefits (eg, gastroprotection that can improve patient tolerance to nonsteroidal anti-inflammatory agents, anti-neuropathic pain, a key component of multimodal analgesia strategy to reduce early postoperative pain, and anti-tumor effects). New delivery systems of tizanidine are developing to improve the pharmacokinetics of oral products, including buccal patches, transdermal delivery systems, nasal spray, and in situ rectal gel. Conclusion Tizanidine is an SMR with unique features and may be an optimal initial choice for older adults. There would be more scientific studies, wider therapeutic applications, and new drug formulations in the future.

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Section: Discussionmentioning

confidence: 99%