THE ABSOLUTE AND RELATIVE BIOAVAILABILITY OF DIPYRIDAMOLE FROM DIFFERENT PREPARATIONS AND THE INVITRO INVIVO COMPARISON

The in vitro liberation and the bioavailability (BV) of dipyridamole (D) in three different brands (A, B, C) were determined in a three way cross-over study on 12 healthy subjects. Also, the pharmacokinetics of D given intravenously was investigated. The in vitro liberation of B is only to be achieved by repeated touching. The tmax for the preparations, expressed as .hivin.x .+-. S.hivin.x amounts as follows: A:0.8 .+-. 0.06; B: 1.1 .+-. 0.1; C: 0.8 .+-. 0.09 hours and is in the case of B significantly different (p < 0.05) from the others. The cmax values (A: 1.01 .+-. 0.25; B: 1.16 .+-. 0.15; C: 1.51 .+-. 0.3 .mu.mol .cntdot. l-1) and the AUC values (A: 3.8 .+-. 0.9; B: 3.1 .+-. 0.5; C: 3.8 .+-. 0.7 .mu.mol .cntdot. h .cntdot. l-1) are not different. The absolute BV of D is 27 .+-. 5.5% (range: 11-44%) independent of the used brand. In 4 subjects a second tmax at the 4th-6th hour is to be observed irrespective of the way of dosing. An enterohepatic circulation is assumed. It is concluded that the determination of the in vitro liberation is a necessary and useful parameter, but cannot be used alone for characterization of the BV in every case, as e.g., for problem drugs.