Pharmacology, electrophysiology, and pharmacokinetics of mexiletine

Woosley, Raymond L.; Wang, T.; Stone, William J.; Siddoway, Lyle A.; Thompson, Katherine A.; Duff, Henry J.; Cerskus, Irene; Roden, Dan M.

doi:10.1016/0002-8703(84)90175-3

Cited by 80 publications

(35 citation statements)

References 22 publications

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“…The mean plasma half-life of mexiletine following oral ingestion is 9–10 h [4]. Agents that alter the pH of urine can influence the half-life of mexiletine, which is shortened when drugs that acidify the urine are co-prescribed and prolonged in urinary alkalisation [5]. Sacubitril/valsartan is freely soluble in water with a pH of 8.2; it can raise the urinary pH which may theoretically potentiate the effects of mexiletine by prolonging its half-life and increasing its plasma concentration with regular mexiletine administration.…”

Section: Discussionmentioning

confidence: 99%

Sacubitril/Valsartan and Mexiletine: A Proarrhythmic Combination?

Weir

2019

Cardiology

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The uptake of sacubitril/valsartan since the PARADIGM study confirmed its beneficial effects on outcomes over enalapril in chronic systolic heart failure has inevitably led to potential interactions with co-prescribed medications in real-world patients. We report two cases that raise the possibility of an interaction between sacubitril/valsartan and the class Ib anti-arrhythmic mexiletine resulting in proarrhythmic effects. We discuss the pharmacokinetics of both agents and posit potential mechanistic interactions that suggest caution should be used and careful monitoring for (ventricular) arrhythmias applied in patients receiving sacubitril/valsartan and mexiletine.

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Section: Discussionmentioning

confidence: 99%

Sacubitril/Valsartan and Mexiletine: A Proarrhythmic Combination?

Weir

2019

Cardiology

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“…The un-ionized fraction of the drug increases in an alkaline medium, so that mexiletine is absorbed mainly from the intestine. If gastric emptying is slowed, and time required for the passage through the stomach is lengthened, the r, , (time required to reach the peak plasma concentration after oral intake) may be prolonged (69).…”

Section: Chemistry and Pharmacokineticsmentioning

confidence: 99%

“…Mexiletine is metabolized more slowly than lidocaine, and the first-pass effect is less than 10% compared to 70% for lidocaine. This difference in metabolism is one of the reasons for the oral effectiveness and long plasma half-life of mexiletine as compared to lidocaine (69).…”

Section: Chemistry and Pharmacokineticsmentioning

confidence: 99%

“…It will be approved for clinical use in the United States in the near future. Since many papers and reviews have already been published to support the effectiveness of mexiletine in arrhythmias, especially of ventricular origin (1,2,19,57,58,69,71), this chapter aims to summarize comparative studies of mexiletine with other antiarrhythmic drugs in order to clarify the pharmacological and therapeutic value of mexiletine compared to other antiarrhythmic drugs.…”

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confidence: 99%

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Mexiletine

Hashimoto¹

1986

Cardiovascular Drug Reviews

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“…2,3) The therapeutic window of mexiletine is narrow, so monitoring of the serum concentration is necessary. 4,5) Congestive heart failure (CHF) may result in altered pharmacokinetics of various drugs.…”

mentioning

confidence: 99%