Effect of diltiazem on plasma concentrations of oxypurines and uric acid

To determine the clinical effect of diltiazem on the metabolism of adenosine, and its importance in ischemic heart disease, arterial plasma concentrations of the purine metabolites were determined in 21 healthy volunteers (10 female and 11 male) and 19 patients with effort angina (8 female and 11 male) before, during, and immediately after standard treadmill exercise tests conducted before and after they had taken 60 mg diltiazem (Cardizem; Hoechst Marion Roussel, Laval, QC, Canada) four times a day for 1 week. The results showed that the cardiac patients had significantly lower mean plasma concentrations of uric acid (46.82 +/- 25.51 versus 95.47 +/- 35.41 micrograms/ml, p 0.05), inosine (0.25 +/- 0.19 versus 0.84 +/- 0.17 microgram/ml, p < 0.05), and hypoxanthine (0.28 +/- 0.35 versus 0.50 +/- 0.27 microgram/ml, p < 0.05). Diltiazem decreased the mean resting plasma concentrations of uric acid in patients (uric acid 43.47 +/- 22.26 versus 46.82 +/- 25.51 micrograms/ml, p < 0.05) and healthy volunteers (uric acid 85.68 +/- 26.71 versus 95.47 +/- 35.41 micrograms/ml, p < 0.05). There was no statistically significant change in the plasma concentrations of the purine metabolites during exercise (p < 0.05). Female subjects had significantly lower plasma concentrations of uric acid than males (patients, 34.87 +/- 26.93 versus 55.78 +/- 21.25 micrograms/ml; healthy volunteers, 84.79 +/- 32.07 versus 104.22 +/- 37.05 micrograms/ml; p < 0.05 for both). Results of the study suggest that normal therapeutic doses of diltiazem may modulate the metabolism of adenosine and that some of the purine metabolites may be useful markers for specific types of ischemic heart disease.