Lidocaine toxicity in a student undergoing upper gastrointestinal endoscopy

Zuberi, Bader Faiyaz; Shaikh, Mamoona; Jatoi, N.-U.-N.; Shaikh, Wazir Muhammad

doi:10.1136/gut.46.3.435

Cited by 19 publications

(1 citation statement)

References 3 publications

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“…Lidocaine solution may also be swallowed before endoscopic procedures. There are several reports of toxicity from orally administered lidocaine, especially in paediatric patients (Hess & Walson 1988; Dawling et al 1989; Gonzalez del Ray et al 1994; Zuberi et al 2000). In the present study the C max of lidocaine after placebo ranged from approximately 50 to 220 ng/ml, and after fluvoxamine alone and together with erythromycin from 110 to 900 ng/ml.…”

Section: Discussionmentioning

confidence: 99%

Effect of Fluvoxamine and Erythromycin on the Pharmacokinetics of Oral Lidocaine

Isohanni

Neuvonen

Olkkola

2006

Basic Clin Pharma Tox

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Lidocaine is metabolized by cytochrome P450 3A4 (CYP3A4) and CYP1A2 enzymes, but inhibitors of CYP3A4 have had only a minor effect on its pharmacokinetics. We studied the effect of co-administration of fluvoxamine (CYP1A2 inhibitor) and erythromycin (CYP3A4 inhibitor) on the pharmacokinetics of lidocaine in a double-blind, randomized, three-way cross-over study. Eight healthy volunteers ingested daily either 100 mg fluvoxamine and placebo, 100 mg fluvoxamine and 1500 mg erythromycin, or their corresponding placebos (control) for five days. On day 6, 1 mg/kg lidocaine was administered orally. Plasma concentrations of lidocaine, monoethylglycinexylidide (MEGX) and 3-hydroxylidocaine (3-OH-lidocaine) were measured for 10 hr. During the fluvoxamine phase the area under the plasma concentration-time curve (AUC) and peak concentration (C max ) of oral lidocaine were 305% (PϽ0.001) and 220% (PϽ0.05) of the control values. During the combination of fluvoxamine and erythromycin, lidocaine AUC was 360% (PϽ0.001) and C max 250% (PϽ0.05) of those during placebo. Fluvoxamine alone had no statistically significant effect on the half-life of lidocaine (t 1/2 ), but during the combination phase t 1/2 (3.8 hr) was significantly longer than during the placebo phase (2.4 hr; PϽ0.01). Fluvoxamine alone and in the combination with erythromycin decreased MEGX peak concentrations by approximately 50% (PϽ0.001) and 30% (PϽ0.01), respectively. We conclude that inhibition of CYP1A2 by fluvoxamine considerably reduces the presystemic metabolism of oral lidocaine and may increase the risk of lidocaine toxicity if lidocaine is ingested. The concomitant use of both fluvoxamine and a CYP3A4 inhibitor like erythromycin may further increase plasma lidocaine concentrations.Lidocaine is an amide-type local anaesthetic widely used for infiltration anaesthesia. It can be applied also to mucous membranes of the oral cavity and ingested after spraying it into the upper respiratory and gastrointestinal tract. Lidocaine is extensively metabolised and only traces are excreted unchanged in urine (Tucker & Mather 1979).Both cytochrome P450 (CYP) 3A4 and 1A2 isoenzymes can be important in the metabolism of lidocaine. The tissue distribution of CYP3A4 and 1A2 is different: CYP3A4 is extensively expressed in the gastrointestinal wall and liver whereas CYP1A2 is mainly located in the liver (Shimada et al. 1994;Kivistö et al. 1996). Accordingly, the relative role of CYP3A4 and 1A2 in lidocaine metabolism can depend on the route of its administration.It has been shown previously that fluvoxamine, a potent inhibitor of CYP1A2 (Brøsen et al. 1993;Rasmussen et al. 1995), considerably decreases the elimination of intravenous lidocaine (Orlando et al. 2004;Olkkola et al. 2005), whereas the strong inhibitors of CYP3A4 erythromycin and itraconazole have only a minor effect (Isohanni et al. 1998). The concomitant inhibition of CYP1A2 and CYP3A4 has affected the pharmacokinetics of intravenous lidocaine

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Section: Discussionmentioning

confidence: 99%

Effect of Fluvoxamine and Erythromycin on the Pharmacokinetics of Oral Lidocaine

Isohanni

Neuvonen

Olkkola

2006

Basic Clin Pharma Tox

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Current Awareness

2000

Pharmacoepidem. Drug Safe.

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of pharmacoepidemiology and drug safety. Each bibliography is divided into 19 sections: 1 Books, Reviews & Symposia; 2 General; 3 Anti‐infective Agents; 4 Cardiovascular System Agents; 5 CNS Depressive Agents; 6 Non‐steroidal Anti‐inflammatory Agents; 7 CNS Agents; 8 Anti‐neoplastic Agents; 9 Haematological Agents; 10 Neuroregulator‐Blocking Agents; 11 Dermatological Agents; 12 Immunosuppressive Agents; 13 Autonomic Agents; 14 Respiratory System Agents; 15 Neuromuscular Agents; 16 Reproductive System Agents; 17 Gastrointestinal System Agents; 18 Anti‐inflammatory Agents ‐ Steroidal; 19 Others. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

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Local anesthetics

2006

Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions

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Lidocaine toxicity in a student undergoing upper gastrointestinal endoscopy

Cited by 19 publications

References 3 publications

Effect of Fluvoxamine and Erythromycin on the Pharmacokinetics of Oral Lidocaine

Effect of Fluvoxamine and Erythromycin on the Pharmacokinetics of Oral Lidocaine

Current Awareness

Local anesthetics

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