INFLUENCE OF FOOD ON THE BIOAVAILABILITY AND SOME PHARMACOKINETIC PARAMETERS OF DIPRAFENONE - A NOVEL ANTIARRHYTHMIC AGENT

Objective:The present study was done to investigate the effect of food on the bioabailability of diprafenone. Methods: The most important ph armacokinetic parameters (C-max,C- t 1/2,C- AUC) and the relative oral availability of a solid oral preparaation of racemic diprafenone were investigated when administered to fasting subjects and 10 min after a standard meal, in an open, randomised, crossover trial. Single oral d oses of 100 mg were given on two different occasions, at least 1 week apart. The serum concentrations of diprafenone and its hydroxy-metabol ite were determined up to 24 hours after administration by a sensitive , specific HPLC method. Fifteen healthy, male volunteers were enrolle d in the trial. Their mean height , weight and age were 183 cm, 80 kg and 22 years, respectively. Fourteen volunteers were found to to rapid hydroxylators and one was a slow hydroxylator of debrisoquine. Only d ata from the rapid hydroxylators were used in the statistical analysis . Results: Food increased the oral bioavailability of diprafenone by a pproximately 50%. This effect was similar in rapid and in slow hydroxy lators. The only slow hydroxylator in this trial had an AUC<INFo-last> /INF ratio (with food/fasting) of 1.54. These findings suggest that di prafenone should be administered in a constant temporal relationship t o food.