Toborinone Otsuka Pharmaceutical Co Ltd.
Toborinone is an inotropic agent with a moderate coronary vasodilatory action, but lacking direct chronotropic action, under development by Otsuka. A marketing application has been filed in Japan [269634], and it has entered phase III trials in the US for the treatment of cardiac failure [170668]. The effects of toborinone in 48 patients with moderate to severe CHF have been evaluated in a multicenter, double-blind study. Patients received either placebo or 1.25, 2.5, 5 or 10 microg/kg/min toborinone via a 6-h infusion. Based on efficacy criteria (25% increase in cardiac index and/or 25% decrease in pulmonary capillary wedge pressure), 25, 58, 92 and 100% of patients receiving 1.25, 2.5, 5 or 10 microg/kg/min toborinone, respectively, had a clinically significant improvement in hemodynamic status after 6 h of infusion, compared to only 17% of patients taking placebo [284078]. A phase I trial of toborinone in 20 healthy Japanese volunteers showed that the drug was well-tolerated. Another phase I trial in 10 patients with congestive heart failure showed that the drug improved ventricular performance without sympathomimetic stimulation of the myocardium [279819]. In anesthetized dogs, the cardiovascular effects of toborinone were unaffected by procainamide and lidocaine, suggesting that it can be used clinically with these antiarrhythmic agents for the treatment of heart failure [175267]. Toborinone did not aggravate adverse effects such as arrhythmias, and can be combined with ACE inhibitors, nitrates and diuretics for the treatment of heart failure [175268].
Kocic
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Department of Pharmacology, Medical University of Gdansk, Poland. ikocic@amg.gda.pl