Enhanced Metabolism of Mexiletine After Phenytoin Administration

Overview

Journal Br J Clin Pharmacol

Specialty Pharmacology

Date 1982 Aug 1

PMID 7104173

Citations 7

Authors

E J Begg

P M Chinwah

C Webb

R O Day

D N Wade

Affiliations

Soon will be listed here.

Abstract

1 Unexpectedly low plasma concentrations of mexiletine were observed in three patients treated with mexiletine and concurrently taking phenytoin. 2 Six healthy volunteers were given a single oral dose of mexiletine (400 mg), before and after 1 week of phenytoin administration (300 mg/day). 3 The mean +/- s.d. area under the plasma mexiletine concentration-time curve decreased from 17.67 +/- 6.21 to 8.01 +/- 3.64 micrograms ml-1 h (P less than 0.003). 4 The mean +/- s.d. half-life of elimination of mexiletine decreased from 17.2 +/- 5.26 to 8.4 +/- 4.17 h (P less than 0.02) 5 The suggested mechanism of the interaction is hepatic mixed-function oxidase enzyme induction by phenytoin. 6 The interaction is likely to be clinically significant.

Citing Articles

Sodium channel slow inactivation as a therapeutic target for myotonia congenita.

Novak K, Norman J, Mitchell J, Pinter M, Rich M Ann Neurol. 2014; 77(2):320-32.

PMID: 25515836 PMC: 4315705. DOI: 10.1002/ana.24331.

Antiarrhythmic agents: drug interactions of clinical significance.

Trujillo T, Nolan P Drug Saf. 2001; 23(6):509-32.

PMID: 11144659 DOI: 10.2165/00002018-200023060-00003.

Clinical pharmacokinetics of mexiletine.

Labbe L, Turgeon J Clin Pharmacokinet. 1999; 37(5):361-84.

PMID: 10589372 DOI: 10.2165/00003088-199937050-00002.

Mexiletine. A review of its therapeutic use in painful diabetic neuropathy.

Jarvis B, Coukell A Drugs. 1998; 56(4):691-707.

PMID: 9806111 DOI: 10.2165/00003495-199856040-00016.

Clinical pharmacokinetics of the newer antiarrhythmic agents.

Gillis A, Kates R Clin Pharmacokinet. 1984; 9(5):375-403.

PMID: 6437721 DOI: 10.2165/00003088-198409050-00001.

References

Talbot R, Nimmo J, Julian D, Clark R, Neilson J, Prescott L . Treatment of ventricular arrhythmias with mexiletine (Kö 1173). Lancet. 1973; 2(7826):399-404. DOI: 10.1016/s0140-6736(73)92270-8. View

Campbell N, Kelly J, Shanks R, Chaturvedi N, Strong J, PANTRIDGE J . Mexiletine (Kö 1173) in the management of ventricular dysrhythmias. Lancet. 1973; 2(7826):404-7. DOI: 10.1016/s0140-6736(73)92271-x. View

Wilkinson G, SHAND D . Commentary: a physiological approach to hepatic drug clearance. Clin Pharmacol Ther. 1975; 18(4):377-90. DOI: 10.1002/cpt1975184377. View

Data J, Wilkinson G, Nies A . Interaction of quinidine with anticonvulsant drugs. N Engl J Med. 1976; 294(13):699-702. DOI: 10.1056/NEJM197603252941305. View

Kelly J . Measurement of plasma mexiletine concentrations. Postgrad Med J. 1977; 53 Suppl 1:48-9. View

Prescott L, Pottage A, Clements J . Absorption, distribution and elimination of mexiletine. Postgrad Med J. 1977; 53 Suppl 1:50-5. View

Kaye C, Kiddie M, Turner P . Variable pharmacokinetics of mexiletine. Postgrad Med J. 1977; 53 Suppl 1:56-9. View

BECKETT A, Chidomere E . The distribution, metabolism and excretion of mexiletine in man. Postgrad Med J. 1977; 53 Suppl 1:60-8. View

Fine A, Henderson I, Morgan D, Tilstone W . Malabsorption of frusemide caused by phenytoin. Br Med J. 1977; 2(6094):1061-2. PMC: 1631827. DOI: 10.1136/bmj.2.6094.1061. View

10.

Campbell N, Kelly J, Adgey A, Shanks R . The clinical pharmacology of mexiletine. Br J Clin Pharmacol. 1978; 6(2):103-8. PMC: 1429421. DOI: 10.1111/j.1365-2125.1978.tb00833.x. View

11.

Campbell N, Kelly J, Adgey A, Shanks R . Mexiletine in normal volunteers. Br J Clin Pharmacol. 1978; 6(4):372-3. PMC: 1429474. DOI: 10.1111/j.1365-2125.1978.tb00868.x. View

12.

Chew C, Collett J, Singh B . Mexiletine: a review of its pharmacological properties and therapeutic efficacy in arrhythmias. Drugs. 1979; 17(3):161-81. DOI: 10.2165/00003495-197917030-00003. View

13.

Johnston A, Burgess C, Warrington S, Wadsworth J, HAMER N . The effect of spontaneous changes in urinary pH on mexiletine plasma concentrations and excretion during chronic administration to healthy volunteers. Br J Clin Pharmacol. 1979; 8(4):349-52. PMC: 1429840. DOI: 10.1111/j.1365-2125.1979.tb04717.x. View

14.

Wing L, Meffin P, Grygiel J, Smith K, Birkett D . The effect of metoclopramide and atropine on the absorption of orally administered mexiletine. Br J Clin Pharmacol. 1980; 9(5):505-9. PMC: 1429945. View

15.

Perucca E, Richens A . Reduction of oral bioavailability of lignocaine by induction of first pass metabolism in epileptic patients. Br J Clin Pharmacol. 1979; 8(1):21-31. PMC: 1429729. DOI: 10.1111/j.1365-2125.1979.tb05904.x. View

16.

Aitio M, Mansury L, TALA E, Haataja M, Aitio A . The effect of enzyme induction on the metabolism of disopyramide in man. Br J Clin Pharmacol. 1981; 11(3):279-85. PMC: 1401616. DOI: 10.1111/j.1365-2125.1981.tb00535.x. View

17.

Routledge P, Stargel W, Finn A, Barchowsky A, SHAND D . Lignocaine disposition in blood in epilepsy. Br J Clin Pharmacol. 1981; 12(5):663-6. PMC: 1401970. DOI: 10.1111/j.1365-2125.1981.tb01286.x. View