Development of a regimen for rapid initiation of perhexiline therapy in acute coronary syndromes

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Perhexiline is a prophylactic anti-anginal agent that ameliorates the metabolic basis for myocardial ischaemia and is increasingly used in the management of acute coro­nary syndromes. No intravenous preparation is available and usual oral loading regimens require 2−3 days to achieve therapeutic drug levels. Two patients presenting to hospital with single-dose over­dosage of perhexiline (6500 mg and 1000 mg, respectively) provided a basis for examining the safety of large single dosage of perhexiline and associated time-course of drug levels. Neither patient had previously taken perhexiline. Peak plasma perhexiline concentrations occurred within 12 h of ingestion and were 2.58 and 0.50 mg/L, respectively (therapeutic range 0.15−0.60 mg/L). The first patient developed transient nausea and vomiting; the second patient had no adverse effects. Subsequently, a series of 10 patients with acute coronary syndromes received an 800-mg loading dose. Peak concentrations occurred within 12 h postdose; the mean levels achieved were 0.40 ± 0.16 mg/L (standard error of the mean). No serious adverse effects were seen. Two patients reported transient nausea or vomiting within 24 h of the loading dose. The utility of this rapid loading regimen for incremental suppression of myocardial ischaemia remains to be assessed. (Intern Med J 2004; 34: 361−363)

Keywords: angina pectoris; overdose; perhexiline; ­pharmacokinetics

Document Type: Research Article


Affiliations: Department of Cardiology and Clinical Pharmacology, Queen Elizabeth Hospital, Adelaide, South Australia, Australia

Publication date: June 1, 2004

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