PHARMACODYNAMICS AND PHARMACOKINETICS OF PINACIDIL AFTER A SINGLE-DOSE OF A NEW SLOW-RELEASE TABLET IN HEALTHY-VOLUNTEERS

Pinacidil (CAS 85371-64-8) is a recently developed antihypertensive dr ug of the class called ''potassium channel openers''. It produces vaso dilatation and a fall of arterial blood pressure. The pharmacokinetics and the pharmacodynamics of pinacidil were studied after single oral administration of a new slow-release tablet formulation (Pindac(TM)) i n comparison to the standard slow-release capsule formulation in healt hy volunteers. Eighteen healthy subjects (3 men and 15 women), with a mean age of 31.1 years were given a single 12.5 mg dose of each formul ation in an open, cross-over study, with randomised sequences and a 7- day wash-out period between doses. Blood samples were collected before and several times up to 36 h after drug administration. Blood pressur e, heart rate and respiratory functions were assessed before and 1, 4, 24 and 36 h-after drug administration. Pinacidil plasma levels were d etermined by HPLC. Both formulations produced a similar significant re duction (10 +/- 4 mmHg) of systolic blood pressure 4 h after administr ation but no changes of diastolic pressure and heart rate. Both the ma ximal effect (E-max) and the area under the effect-time curve (AUEO-36 ) were similar for the two formulations. The main model-independent ph armacokinetic parameters of Pinacidil (C-max, T-max, AUC, MRT) as well as the absorption and the elimination half-lives were similar after t he two formulations. The main advantage of the tablet formulation comp ared to the capsules is that tablets can be easily cut and therefore t he dosage can be adapted to an individual patient's needs.