Pharmacokinetic and bioavailability of diltiazem sustained-release: influence of food and time of administration

Summary— Diltiazem is a calcium channel blocking agent known to be effective in the treatment of angina pectoris, hypertension and supraventricular arrhythmias. To improve the conditions of diltiazem administration in the treatment of hypertensive patients, a sustained-release formulation (Mono-Tildiem® LP 300 mg) allowing a single daily oral administration has been developed. The aim of the present study was to first evaluate the influence of food intake and second to evaluate those of the time of administration on the pharmacokinetic parameters and the bioavailability of this sustained-release formulation. The influence of these factors was investigated over two different open, randomized, cross-over studies in 12 healthy volunteers. Although a significant decrease in Tmax and an increase in Cmax occurred when diltiazem sustained-release was administered with food intake, AUC_0–48, and therefore the fraction absorbed, were not modified either by concurrent food intake or by different times of administration. The minor modifications of pharmacokinetic parameters of diltiazem sustained release observed were unlikely to induce any clinical consequence.