1Mexiletine was given to 156 patients by intravenous or oral routes of administration. 2 There was great interpatient variation in kinetics and plasma concentrations with both routes of administration. 3 The mean volume of distribution was 6.63 1/kg. The mean plasma elimination half-life after chronic oral therapy was 11.31 h.4 Plasma concentrations between 0.75 and 2.00 gg/ml were usually effective. Within this therapeutic range severe side effects were uncommon. 5Plasma concentrations within this range were achieved in 72% of patients when doses of 10-14 mg-' kg-l day were given orally.

SUMMARY Forty-eight patients with ischaemic heart disease received oral mexiletine for the control or prevention of ventricular arrhythmias.

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suMMARY The haemodynamic effects of intravenous mexiletine have been studied in 16 patients with valvular heart disease without clinical evidence of heart failure.A bolus injection of 150 mg administered to 6 of the 16 patients resulted in a mean plasma concentration above the therapeutic range for at least 5 minutes after the drug was given. A small but significant rise in the mean pulmonary artery pressure occurred.In 10 patients, the effects of intravenous mexiletine were compared with those of intravenous saline in a double blind trial. No significant difference was found in the haemodynamic effects, though both saline and mexiletine produced a small rise in the mean pulmonary artery pressure.Mexiletine when administered to patients without heart failure in doses known to be clinically effective did not have important adverse haemodynamic effects.Mexiletine, a relatively new antiarrhythmic drug, when given intravenously controls ventricular arrhythmias . Adverse haemodynamic effects were not observed when doses of from 50 to 140 mg were injected intravenously (Banim et al., 1977;Pozenel, 1977). These doses are smaller than those used in clinical practice Prescott, 1977). Preliminary studies from our laboratory showed a statistically significant fall in cardiac index and a rise in systemic vascular resistance in patients receiving 100 mg mexiletine intravenously (Campbell, 1976).The investigation reported here was designed to clarify the haemodynamic effects of mexiletine given in bolus injections which are clinically effective.

Clinical uses for recombinant human erythropoietin (rHuEPO) therapy continue to expand. Initial use was in anaemia associated with end-stage renal disease, but more recently there have been many reports of the benefits of erythropoietin in other clinical situations such as cancer-related anaemia. Recombinant erythropoietin reduces the need for blood transfusion and hence exposure to donor blood products as well as improving quality of life. We report four patients who were transfusion dependent, none of whom had licensed indications for the use of recombinant erythropoietin. Two patients had microangiopathic haemolytic anaemia secondary to mechanical valve haemolysis and were unsuitable for any further cardiac intervention. One patient had anaemia of chronic disease and anti-Vel red cell antibodies, making compatible blood transfusions difficult to obtain. The fourth patient had primary thrombocythaemia and developed transfusion-dependent anaemia secondary to myelosuppressive agents. All four patients had a relative deficiency in endogenous erythropoietin levels ranging between 7 and 41 IU/l. After commencing recombinant erythropoietin therapy, all had a response in haemoglobin of at least 1 g/dl with an overall improvement in their quality of life. We conclude that rHuEPO is a very convenient and useful form of treatment in transfusion-dependent anaemia and in some cases beyond the licensed indications.