Response to “Commentary on ‘Influence of Food on the Bioavailability of Verapamil’ ”

To the Editor: The letter of Messina and De Vito discusses our results on the effect of food on the bioavailability of sustained-release verapamil (240 mg; SR-verapamil, Isoptin-SR, Knoll) as they relate to results obtained by themselves, another literature report, and to the information in the package insert for Isoptin-SR (from the USA). The first point they make is that the Cmax values determined in our study are much lower than those determined from other studies. The Cmax values obtained in our study, in the sources provided by Messina and De Vito, and in other studies referenced in our original paper are shown in Table I. It is clear, first of all, that interindividual variability of this parameter is high, with coefficients of variation of the Cmax in the range 41–86%. In fact, the Cmax obtained for 240 mg of Isoptin-SR in our study is not significantly different from that obtained by Messina and De Vito (two-sample t test, p > 0.1), largely because of this variability. It is also clear that the Cmax determined in our study is not ‟much lower than one would expect”, but rather is mid-range of the values reported in the literature for this formulation of verapamil. The AUC0–∞ values determined in the different studies are remarkable for their consistency.