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 drug of the class called "potassium channel openers". It produces vasodilatation 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) in comparison to the standard slow-release capsule formulation in healthy 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 formulation 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 pressure, heart rate and respiratory functions were assessed before and 1, 4, 24 and 36 h-after drug administration. Pinacidil plasma levels were determined by HPLC. Both formulations produced a similar significant reduction (10 +/- 4 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 (AUE0-36) were similar for the two 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.
Department of Pharmacology, Medical School, University of Milan, Italy.
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Bareggi
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Gambaro
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Valenti
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Benvenuti
D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D020110:Pinacidil; D012129:Respiratory Function Tests
D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D006146:Guanidines; D020110:Pinacidil