Pharmacodynamics and pharmacokinetics of pinacidil after a single dose of a new slow-release tablet in healthy volunteers

The pharmacokinetics and the pharmacodynamics of the antihypertensive K channel opener pinacidil were studied after single oral administration of a slow-release tablet formulation (Pindac) in comparison to the std. slow-release capsule formulation in healthy volunteers. Healthy subjects with a mean age of 31.1 yr were given a single 12.5 mg dose of each formulation in an open, cross-over study, with randomized sequences and a 7-day wash-out period between doses. Blood samples were collected before and several times ≤36 h after drug administration. Blood pressure, heart rate, and respiratory functions were assessed before and 1, 4, 24, and 36 h-after drug administration. Pinacidil plasma levels were detd. by HPLC. Both formulations produced a similar redn. (10 mmHg) of systolic blood pressure 4 h after administration but no changes of diastolic pressure and heart rate. Both the maximal effect (Emax) and the area under the effect-time curve (AUEQ0-36) were similar for the 2 formulations. The main model-independent pharmacokinetic parameters of Pinacidil (Cmax, Tmax, AUC, MRT) as well as the absorption and the elimination half-lives were similar after the two formulations. The main advantage of the tablet formulation compared to the capsules is that tablets can be easily cut and therefore the dosage can be adapted to an individual patient's needs.