Effects of formulation on the pharmacokinetics of orally administered pinacidil in humans.

Serum concentrations, relative bioavailability, and urinary excretion of pinacidil [(+/-)-2-cyano-1-(4-pyridyl)-3-(1,2,2-trimethylpropyl) guanidine monohydrate] from two sustained-release oral formulations (tablet and capsule) were compared in 12 healthy volunteers. Maximum measured serum concentrations (Cmax) from the sustained-release tablet and capsule did not differ significantly (75 +/- 17 versus 70 +/- 14 ng/mL, p greater than 0.05), but the time to achieve maximum concentration (tmax), was longer for the capsule (2.4 +/- 1.8 versus 0.98 +/- 0.5 h, p less than 0.05). There was no significant difference in bioavailability between the formulations, as measured by the area under the concentration-time curve (AUC0-8 h; 279 +/- 99 versus 311 +/- 85 ng.h/mL, p greater than 0.05). Twenty-four hour urinary excretion of both pinacidil and its major metabolite, pinacidil pyridine-N-oxide, was similar for both tablet and capsule preparations (3.9 +/- 1.2 and 55 +/- 19% versus 4.4 +/- 1.0 and 55 +/- 14%, respectively, of the administered dose, p greater than 0.05).