ABSORPTION AND BIOAVAILABILITY OF PENTAERITHRITYL-TETRANITRATE (PETN,DILCORAN-80)

The effects of 80 mg pentaerithrityl-tetranitrate (PETN) as suspension or formulated as tablets were compared to placebo in a single blind, randomized, crossover study in 18 healthy subjects (study A), and the bioequivalence of two tablet formulations (marketed Dilcoran 80 vs a n ew formulation) was studied in 24 healthy subjects after administratio n of single oral doses of 80 mg PETN according to a placebo controlled , randomized, double blind, two-way crossover study design (study B). The perfusion of the right middle finger was measured by rheography (a ltitude A of the changes of resistance and of the incisure D) before a nd 24 h post-dose, and blood pressure and heart rate were measured in supine position at the same time. The values of area under curve (AUG) of the ratio A/D were calculated by the trapezoidal rule. In study A the mean A/D-values were reduced from about 2.0 to about 1.3 after int ake of PETN (solution or tablet) with a minimum 60 to 90 min postdose (solution) and 2 h postdose (tablet). A significant reduction in this ratio was seen up to 8 (solution) or 12 h (tablet) post dose. Changes in blood pressure were not observed while the heart rate decreased in the subjects of all three groups 1 to 2 h postdose followed by an incr ease by 6 to 10 beats per min. After subtraction of the AUC values of placebo from the PETN-derived AUC values, mean values of 6.61 (SD 1.52 , solution) and 7.25 (SD 1.48, A/Dh, tablet) were calculated (p > 0.1 , study A). In study B mean effect AUC values far the two PETN tablets were 12.39 and 12.35 (A/Dh), respectively. A comparable extent of ef fect of the two PETN tablet formulations was found measured in terms o f A/D values. The maximum effect of the tablet formulations (1.29 vs 1 .27, A/D) occurred 3.75 h (marketed tablet) or 4.04 h (''new'' formula tion) postdose. The effect time curves were similar. Westlake's 90% co nfidence interval for effect AUC was 90.3 to 109 and for maximum effec t 94.1 to 102%, respectively. Thus, the two tablet formulations were b ioequivalent (study B).