Effect of CYP Inducers/Inhibitors on Topiramate Concentration: Clinical Value of Therapeutic Drug Monitoring

Abbreviations: AUC, area under the plasma concentration-time curve; AUCR, ratio of AUC in presence to absence of inhibitor; CYP, cytochrome P450; DEA, Drug Enforcement Administration; f u,p , fraction unbound in human plasma; HIMs, human intestinal microsomes; HLMs, human liver microsomes; IVIVE, in vitro to in vivo extrapolation; k inact , maximum rate of inactivation; K I , time-dependent inhibition constant; K i , reversible inhibition constant; TDI, timedependent inhibition; UPLC-MS/MS, ultra-high performance liquid chromatography-tandem mass spectrometry This article has not been copyedited and formatted. The final version may differ from this version.

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“…Oxycodone, tramadol, topiramate, diphenhydramine, zolpidem CYP3A, CYP2D6 (Pichard et al, 1995;Miotto et al, 2017;Yamamoto et al, 2017) 6…”

Section: Figure Legendsmentioning

confidence: 99%

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations

Tanna

Tian

Cech

et al. 2020

J Pharmacol Exp Ther

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“…None of the four drugs affect the action of P-glycoprotein. There are no data on possible interactions between mexiletine and pregabalin, topiramate, lamotrigine or oxcarbazepine [ 58 – 64 ].…”

Section: Discussionmentioning

confidence: 99%

Interactions of Mexiletine with Novel Antiepileptic Drugs in the Maximal Electroshock Test in Mice: An Isobolographic Analysis

et al. 2018

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The aim of the study was to evaluate precisely the type of interactions between mexiletine (an antiarrhythmic drug) and four new generation antiepileptic drugs: lamotrigine, oxcarbazepine, topiramate and pregabalin in the maximal electroshock test in mice (MES). The isobolographic analysis was used to assess the nature of interactions between the tested drugs. Total brain concentrations of antiepileptics were also measured to detect possible pharmacokinetic interactions. The results obtained indicated that the mixture of mexiletine and pregabalin at the fixed ratios of 1:1 and 3:1 led to supra-additive interaction in terms of seizure suppression, while the proportion of 1:3 occurred additive. Synergism was also demonstrated for the combination of mexiletine and topiramate in all three proportions. Combinations of mexiletine with lamotrigine and mexiletine with oxcarbazepine were found to be additive. Adverse-effect profiles of mexiletine, antiepileptics and drug combinations were evaluated in the chimney test (motor coordination) and step-through passive-avoidance task (long-term memory). Mexiletine and drug combinations did not impair long-term memory. Moreover, all combinations of mexiletine with lamotrigine, oxcarbazepine and topiramate had no significant effect on motor coordination. However, the results from the chimney test indicated that pregabalin, administered alone at its ED50 dose from the MES-test, significantly impaired motor performance. Similar adverse effects were observed when mexiletine was co-administered with pregabalin at the fixed-dose ratio combinations of 1:1 and 1:3. However, reduction of pregabalin dose at the fixed ratio of 3:1 seems to prevent significant motor impairment. The results may indicate that mexiletine can be considered as an adjunctive drug in antiepileptic treatment, particularly in patients with concomitant cardiac arrhythmia.

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“…According to the package insert (Topina, Kyowa Hakko Kirin, Japan), this drug is chiefly metabolized by CYP3A4. Stiripentol is a potent inhibitor of CYP3A4, but interactions between topiramate and stiripentol have not been studied 82…”

Section: Topiramatementioning

confidence: 99%

<p>Pharmacogenetics of alcohol addiction: current perspectives</p>

Застрожин¹,

Skryabin²,

Miroshkin³

et al. 2019

TACG

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Genetics of alcohol addiction is currently a contradictive and complex field, where data in the most studies reflect methods’ limitations rather than meaningful and complementary results. In our review, we focus on the genetics of alcohol addiction, leaving genetics of acute alcohol intoxication out of the scope. A review of the literature on pharmacogenetic biomarkers development for the pharmacotherapy personalization reveals that today the evidence base concerning these biomarkers is still insufficient. In particular, now the researches with the design of randomized controlled trials and meta-analysis investigating the effect of the SNPs as biomarkers on the therapy efficacy are available for naltrexone only. For other medications, there are only a few studies in small samples. It decreases the possibilities to implement the pharmacogenetic algorithms for the pharmacotherapy personalization in patients with alcohol use disorders (AUD). In view of the importance of the precision approaches development not in addiction medicine only, but in other fields of medicine also to increase the efficacy and safety of the therapy, studies on pharmacogenetic biomarkers development for the medications used in patients with AUD (eg, naltrexone, disulfiram, nalmefene, acamprosate, etc.) remain relevant to this day.

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Effect of CYP Inducers/Inhibitors on Topiramate Concentration: Clinical Value of Therapeutic Drug Monitoring

Abstract: Concomitant use of hepatic enzyme inducers markedly reduced the plasma TPM concentration and can decrease its antiepileptic effect. A therapeutic concentration of >5 mcg/mL TPM was significantly associated with continuation of therapy, and therapeutic drug monitoring can be helpful.

Cited by 13 publications

References 19 publications

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations

Interactions of Mexiletine with Novel Antiepileptic Drugs in the Maximal Electroshock Test in Mice: An Isobolographic Analysis

<p>Pharmacogenetics of alcohol addiction: current perspectives</p>

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