Possible mechanism for pharmacokinetic interaction between lidocaine and mexiletine

Maeda, Yorinobu; Funakoshi, Sachiyo; Nakamura, Mamoru; Fukuzawa, Masataka; Kugaya, Yukimasa; Yamasaki, Miho; Tsukiai, Satsuki; Murakami, Teruo; Takano, Mikihisa

doi:10.1067/mcp.2002.124077

Cited by 18 publications

(7 citation statements)

References 18 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the detected levels of lidocaine in the brain were consistent with the fact that 500 mg of lidocaine was administered and this overdose must have been the cause of hypoxic encephalopathy. Metabolism of lidocaine may be delayed under the critical conditions and/or due to drug interaction between lidocaine and mexiletine (Maeda et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

3. A Fatal Case of Poisoning by Lidocaine Overdosage – Analysis of Lidocaine in Formalin-Fixed Tissues

et al. 2004

View full text Add to dashboard Cite

The death of a 76-year-old man with heart disease as a result of the injection of an excessive dose of lidocaine is presented. The patient was given 5 ml of 10% lidocaine hydrochloride (500 mg) intravenously instead of 2.5 ml of 2% lidocaine hydrochloride (50mg) in order to treat repeated paroxysmal ventricular arrhythmia. Immediately following the injection the patient had tonic clonic seizures and complete cardiopulmonary arrest followed. Although resuscitation attempts once successfully restarted his pulse and spontaneous respiration, the patient died on the eighth day after the injection. Toxicological examinations were carried out on the tissues obtained at the time of autopsy and which had been fixed in formalin solution for 40 days, and lidocaine was detected in each tissue examined. The concentrations were (ng/g or ml): parietal lobe, 308.0; occipital lobe, 208.7; temporal lobe, 318.0; frontal lobe, 223.2; cerebellum 200.9; pons 285.7; liver, 109.5; kidney 52.2; skeletal muscle 127.0; and formalin solution 8.4. In an experiment on rats we determined the concentration changes of lidocaine in formalin fixed tissues. The concentrations of lidocaine in these tissues significantly decreased to 1/3-1/4 from the original. This data shows that the cause of death was poisoning by lidocaine overdose.

show abstract

Section: Discussionmentioning

confidence: 99%

3. A Fatal Case of Poisoning by Lidocaine Overdosage – Analysis of Lidocaine in Formalin-Fixed Tissues

et al. 2004

View full text Add to dashboard Cite

show abstract

“…The dosing conversion from IV lidocaine to mexiletine is unclear, but patients who tolerate IV lidocaine well can probably take a higher mexiletine dose. Due to potential for significant interactions, including neurotoxicity, mexiletine should not be given to patients receiving IV lidocaine [20]. Taking mexiletine with food may reduce the incidence of nausea or heartburn, the most common AEs [22].…”

Section: Intravenous Lidocaine and Mexiletine: Practical Considerationsmentioning

confidence: 99%

“…Hepatic impairment, inhibitors of CYP2D6 (including duloxetine, bupropion, fluoxetine, and citalopram), and CYP1A2 inhibitors (eg, verapamil, fluvoxamine, and ciprofloxacin) may increase serum levels and toxicity. Mexiletine interacts with lidocaine by displacing lidocaine from binding sites, increasing levels and toxicity [20]. Metabolites of mexiletine have minimal antiarrhythmic activity [15].…”

Section: Intravenous Lidocaine and Mexiletine: An Overviewmentioning

confidence: 99%

Intravenous Lidocaine and Mexiletine in the Management of Trigeminal Autonomic Cephalalgias

Marmura

2010

Curr Pain Headache Rep

View full text Add to dashboard Cite

Lidocaine and mexiletine are class 1B antiarrhythmic drugs that act on sodium channels. Lidocaine is also an important anesthetic and topical agent that is useful in the treatment of multiple pain disorders, and mexiletine is commonly used for neuropathic pain and myotonia. Both intravenous lidocaine and mexiletine are increasingly used to treat pain syndromes and appear to be particularly effective in neuropathic pain. This suggests a role for these agents in patients with headache disorders. This article describes the role of intravenous lidocaine and mexiletine in the management of headache and trigeminal autonomic cephalalgias based on the published literature to date and provides practical guidelines for their use.

show abstract

“…1) are the major antiarrhythmic agents administered for the treatment of cardiovascular diseases. The therapeutic concentration ranges of these two agents in serum are narrow, being 3–11 μM and 6–21 μM for mexiletine and lidocaine, respectively . Thus, elevated concentrations of these agents can cause significant toxicity, and underdosing results in ineffective treatment .…”

Section: Introductionmentioning

confidence: 99%

Surfactant‐assisted dispersive liquid–liquid microextraction combined with field‐amplified sample stacking in capillary electrophoresis for the determination of mexiletine and lidocaine

Yeh

Chen

Chang

2017

J of Separation Science

View full text Add to dashboard Cite

A sensitive method for the determination of mexiletine and lidocaine using surfactant-assisted dispersive liquid-liquid microextraction coupled with capillary electrophoresis was developed. Triton X-100 and dichloromethane were used as the dispersive agent and extraction solvent, respectively. After the extraction, mexiletine and lidocaine were analyzed using capillary electrophoresis with ultraviolet detection. The detection sensitivity was further enhanced through the use of field-amplified sample stacking. Under optimal extraction and stacking conditions, the calibration curves were linear over a concentration range of 0.05-1.00 μM for mexiletine and 0.03-1.00 μM for lidocaine. The limits of detection (signal-to-noise ratio of 3) were 0.01 and 0.01 μM for mexiletine and lidocaine, respectively. An approximately 1141- to 1250-fold improvement in sensitivity was observed for the two analytes compared with the injection of a standard solution without the surfactant-assisted dispersive liquid-liquid microextraction and field-amplified sample stacking procedures. This developed method was successfully applied to the determination of mexiletine and lidocaine in human urine and serum samples. Both precision and accuracy for urine and serum samples were less than 8.7 and 6.7%, respectively. The recoveries of the two analytes from urine and serum samples were 54.7-64.9% and 16.1-56.5%, respectively.

show abstract

Possible mechanism for pharmacokinetic interaction between lidocaine and mexiletine

Cited by 18 publications

References 18 publications

3. A Fatal Case of Poisoning by Lidocaine Overdosage – Analysis of Lidocaine in Formalin-Fixed Tissues

3. A Fatal Case of Poisoning by Lidocaine Overdosage – Analysis of Lidocaine in Formalin-Fixed Tissues

Intravenous Lidocaine and Mexiletine in the Management of Trigeminal Autonomic Cephalalgias

Surfactant‐assisted dispersive liquid–liquid microextraction combined with field‐amplified sample stacking in capillary electrophoresis for the determination of mexiletine and lidocaine

Contact Info

Product

Resources

About