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  • Title: Comparison of the plasma concentrations and efficacy of mexiletine and of a slow-release preparation of mexiletine in patients admitted to a coronary care unit.
    Author: Boyle DM, Barber JM, Chapman C, Khalid I, Kinney CD, McIlmoyle EL, Salathia K, Shanks RG.
    Journal: J Cardiovasc Pharmacol; 1982; 4(2):174-9. PubMed ID: 6175798.
    Abstract:
    We determined if therapeutic plasma concentrations of mexiletine (0.75-2.0 microgram/ml) could be maintained in patients admitted to a coronary care unit by twice daily dosing of a new slow-release (S.R.) formulation of mexiletine. Twenty patients, 14 with acute myocardial infarction, entered the first study and received either 250 mg conventional mexiletine at 0.8, and 14 h or 360 mg S.R. mexiletine at 0 and 12 h each day for 7 days. Blood samples were taken daily for measurement of plasma mexiletine concentrations. A continuous 24 -h ECG recording was obtained in all patients between days 3 and 6. The mean plasma concentration was greater on all days in the group that received conventional mexiletine; these differences were most marked during the first 15 h on day 1. The mean trough values on days 2-7 were in the range 0.73-1.22 microgram/ml after mexiletine and 0.63-1.17 microgram/ml after S.R. mexiletine. The incidence of ventricular arrhythmias was the same in the two groups; side effects were less common in the group receiving S.R mexiletine. Since the plasma concentration increased slowly during day 1 with S.R. mexiletine, a second study was carried out in 19 similar patients who received 360 mg S.R. mexiletine, 720 mg S.R. mexiletine, or 360 mg S.R. mexiletine and 250 mg conventional mexiletine and 12 h later 360 mg S.R. mexiletine. The plasma concentration increased most rapidly after the third regime, reaching 0.97 +/- 0.09 microgram/ml at 3 hours. These results show that therapeutic plasma concentrations of mexiletine can be maintained by the 12-hourly administration of 360 mg S.R. mexiletine, but that an additional loading dose of 250 mg mexiletine increases the plasma concentration more rapidly.
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