Yeung P K, Buckley S J, Hung O R, Pollak P T, Barclay K D, Feng J D, Klassen G A
College of Pharmacy, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Ther Drug Monit. 1997 Jun;19(3):286-91. doi: 10.1097/00007691-199706000-00008.
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.
为了确定地尔硫䓬对腺苷代谢的临床效果及其在缺血性心脏病中的重要性，在21名健康志愿者（10名女性和11名男性）和19名劳力性心绞痛患者（8名女性和11名男性）中，于服用60毫克地尔硫䓬（恬尔心；赫斯特马里昂罗塞尔公司，加拿大魁北克省拉瓦尔）每日4次，共1周前后，在标准平板运动试验前、试验期间及试验后即刻，测定嘌呤代谢产物的动脉血浆浓度。结果显示，心脏病患者的尿酸平均血浆浓度（46.82±25.51对95.47±35.41微克/毫升，p<0.05）、肌苷（0.25±0.19对0.84±0.17微克/毫升，p<0.05）和次黄嘌呤（0.28±0.35对0.50±0.27微克/毫升，p<0.05）显著更低。地尔硫䓬降低了患者（尿酸43.47±22.26对46.82±25.51微克/毫升，p<0.05）和健康志愿者（尿酸85.68±26.71对95.47±35.41微克/毫升，p<0.05）的静息血浆尿酸平均浓度。运动期间嘌呤代谢产物的血浆浓度无统计学显著变化（p<0.05）。女性受试者的尿酸血浆浓度显著低于男性（患者，34.87±26.93对55.78±21.25微克/毫升；健康志愿者，84.79±32.07对104.22±37.05微克/毫升；两者均p<0.05）。研究结果表明，地尔硫䓬的正常治疗剂量可能调节腺苷代谢，且一些嘌呤代谢产物可能是特定类型缺血性心脏病的有用标志物。
