CardizemOSR and Bi-TildiemO were both approved in their respective countries on the basis of clinical trials demonstrating efficacy and safety in the treatment of angina pectoris. In this cross-over randomized study, we assessed whether these two sustained-release formulations of diltiazem have equivalent pharmacokinetic and pharmacodynamic profiles. Twenty-four young healthy male volunteers were hooked to Holters and ambulatory blood pressure monitors for 24 h to establish baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), sinus rate and PR intervals. They then received a single dose of 120mg of diltiazem from one formulation. The pharmacodynamic measurements were recorded for a further 24 h and blood samples were collected over 36 h for evaluation of diltiazem in plasma by a high-performance liquid chromatographic (HPLC) method. The procedures were repeated with the alternate formulation after a 7 d wash-out. Pharmacokinetics showed statistically significant ( p < 0.01) differences in AUCo-,, with means (k SD) of 519*2( & 172-8) and 429.6(& 147-2) ng h rnl-], AUCo-,, of 835-6(2281.6) and 730-9 (+271*5)nghml-' and C,, of 89-1(?30-3) and 61 * I ( 2 21 -2) ng ml-' for CardizemOSR and Bi-Tildiem@, respectively. The only pharmacodynamic parameter showing a statistically significant difference in change from baseline between the two formulations was DBP with mean (+SD) change in AUC,-,, of -13.6(*20.8) and +8-4(&31.7)mrnHgh (p=0.0135) and in AUC0-*, of -33-0(?43.7) and -0*3(?59*2)mmHg h (p=0.0463) for CardizemO'SR and Bi-TildiemO, respectively. These findings suggest that assessment of efficacy of sustainedrelease formulations of diltiazem by bioequivalence could be misleading. They also confirm that a single dose of diltiazem does not elicit a significant pharmacodynamic response in healthy volunteers. Equivalence for such formulations should therefore be demonstrated by pharmacodynamic evaluation or clinical studies in a patient population.