The appropriate dosage regime for the transition from intravenous lignocaine to oral tocainide after acute myocardial infarction

Summary To define the appropriate regime for the transition from intravenous lignocaine to oral tocainide after uncomplicated acute myocardial infarction, 43 patients received lignocaine to steady state. Each patient then received a tocainide dosage schedule. Plasma concentration of lignocaine and tocainide was measured frequently until the third peak plasma tocainide level. Tocainide 400 mg 8 hourly starting 4 h before cessation of lignocaine and tocainide 400 mg 4 hourly starting at the end of the infusion produced therapeutic plasma tocainide concentration (3.5–9 mg/l) only after the second dose. Tocainide 600 mg 12 hourly starting 6 h before cessation of lignocaine and tocainide 600 mg 6 hourly starting at the end of the infusion quickly achieved therapeutic plasma tocainide concentration which declined to give subtherapeutic first dose troughs of 2.42 mg/l (±0.28 SEM) and 2.79 mg/l (±0.27 SEM) respectively. Consistently therapeutic plasma tocainide concentrations were achieved by both of these regimes after the second dose. The short plasma halflife of lignocaine which for these regimes was 3.71 h (±0.25 SEM), resulted in subtherapeutic lignocaine concentrations before consistently therapeutic plasma tocainide concentrations had been achieved. On the basis of these results, the 600 mg 6 hourly tocainide dosage schedule was studied with cessation of lignocaine infusion either two or six h after the first tocainide dose. With the former regime only three of 5 patients had therapeutic lignocaine at the subtherapeutic tocainide trough. When lignocaine was discontinued on administration of the second tocainide dose however, therapeutic lignocaine concentration was maintained in all patients until tocainide was rising within the therapeutic range. The latter regime, which we would recommend, was not accompanied by increased side effects. Steady state tocainide was found to be present 12 h after the third tocainide dose allowing continued therapy with tocainide 600 mg 12 hourly.