EFFICACY AND PHARMACOKINETICS OF GALLOPAMIL IN PATIENTS WITH CORONARY-ARTERY DISEASE

We prospectively studied 10 patients with stable exertional ischaemia, selected from a larger group of patients referred for suspected coron ary artery disease or to detect residual ischaemia after myocardial in farction, to evaluate pharmacokinetic changes during chronic treatment with gallopamil and its correlation with clinical efficacy in patient s with coronary artery disease. Our study consisted of a 1-week run-in single-blind placebo treatment and a 4-week single-blind gallopamil t reatment. At the end of the run-in period patients underwent two diffe rent exercise tests, the first 2 hours and the second 7 hours after pl acebo administration. During active treatment all patients underwent t wo different exercise tests, the first 2 hours and the second 7 hours after gallopamil (50 mg) administration on the Ist and 28th days of ga llopamil therapy. On the same days in eight of the patients we evaluat ed gallopamil pharmacokinetic changes. Our data revealed a rapid incre ase of unchanged gallopamil and its metabolite (norgallopamil) in the plasma, and a peak concentration of these substances about 2 hour afte r oral administration on both the Ist and 28th day of observation. Mor eover, our results demonstrated an increase between the first and 28th day of treatment in peak concentration of unchanged gallopamil in the plasma, and of AUC 0-infinity and AUC o-c values during chronic treat ment with gallopamil. Our clinical data showed an improvement in exerc ise results during gallopamil therapy related to increased concentrati on of the drug. (C) 1996 The Italian Pharmacological Society