Pharmacodynamics and pharmacokinetics of pinacidil in normotensive volunteers after repeated doses of a new slow-release tablet formulation

Pinacidil (CAS 85371-64-8) is an antihypertensive drug of the class of agents called "potassium channel openers". The pharmacokinetics were studied after repeated oral administration of a new slow release tablet formulation (Pindac) as compared with the std. slow release capsule formulation in healthy volunteers. 18 Healthy volunteers (3 males and 15 females), aged from 22-48 yr, and 49-95 kg in wt., were given a 12.5 mg dose of each formulation every 12 h for 7 days on 2 occasions, in a randomized, cross-over trial with at least 2 wk interval between trials. Blood samples were drawn immediately before drug administration on the morning of days 1, 2, 3, 4, 5, 6, and 7 and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 36 h after the last drug administration. Blood pressure, heart rate, and respiratory function were assessed at adminission and on the morning of day 0 (baseline), 2 and 7, before drug administration, and at 4, 24 and 36 h after the final administration. Pinacidil plasma levels were detd. by, an HPLC method. Both formulations elicited similar redns. of systolic and diastolic pressures from 4 h after administration, but did not change heart rate. The main model-independent pharmacokinetic parameters of pinacidil (Cmax, Tmax, AUC, MRT), as well as the absorption and elimination half-lives were similar with the 2 formulations. During the study there were no complaints of side-effects with either of the formulations. One advantage of the new formulation as compared to the capsules is that the tablets can be cut easily and the dosage adapted to a patient's needs.