Martin Paul D, Schneck Dennis W, Dane Aaron L, Warwick Michael J
AstraZeneca, Alderley Park, Cheshire, UK.
Curr Med Res Opin. 2008 Apr;24(4):1231-5. doi: 10.1185/030079908x280662. Epub 2008 Mar 19.
Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor used for the treatment of dyslipidaemia, may be co-administered with antacids in clinical practice. This trial assessed the effect of simultaneous and separated administration of an antacid preparation containing aluminium hydroxide 220 mg/5 mL and magnesium hydroxide 195 mg/5 mL (co-magaldrox 195/220) on the pharmacokinetics of rosuvastatin.
A randomised, open-label, three-way crossover trial was performed. Healthy male volunteers (n = 14) received a single dose of rosuvastatin 40 mg alone, rosuvastatin 40 mg plus 20 mL antacid suspension taken simultaneously, and rosuvastatin 40 mg plus 20 mL antacid suspension taken 2 h after rosuvastatin on three separate occasions with a washout of > or = 7 days between each.
The primary parameters were area under the rosuvastatin plasma concentration-time curve from time zero to the last quantifiable concentration (AUC(0-t)) and maximum observed rosuvastatin plasma concentration (C(max)) in the absence and presence of antacid.
When rosuvastatin and antacid were given simultaneously, the antacid reduced the rosuvastatin AUC(0-t) by 54% (90% confidence interval [CI] for the treatment 0.40-0.53) and C(max) by 50% (90% CI 0.41-0.60). When the antacid was given 2 h after rosuvastatin, the antacid reduced the rosuvastatin AUC(0-t) by 22% (90% CI 0.68-0.90) and the C(max) by 16% (90% CI 0.70-1.01). The effect of repeated antacid administration was not studied and it cannot be discounted that this may have resulted in a stronger interaction than that observed here.
Simultaneous dosing with rosuvastatin and antacid resulted in a decrease in rosuvastatin systemic exposure of approximately 50%. This effect was mitigated when antacid was administered 2 h after rosuvastatin.
瑞舒伐他汀是一种用于治疗血脂异常的3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂，在临床实践中可能会与抗酸剂联合使用。本试验评估了含220 mg/5 mL氢氧化铝和195 mg/5 mL氢氧化镁的抗酸制剂（复方铝镁加195/220）同时给药和分开给药对瑞舒伐他汀药代动力学的影响。
进行了一项随机、开放标签、三交叉试验。健康男性志愿者（n = 14）在三个不同时间分别接受单剂量40 mg瑞舒伐他汀、40 mg瑞舒伐他汀加20 mL抗酸混悬液同时服用，以及40 mg瑞舒伐他汀加20 mL抗酸混悬液在瑞舒伐他汀服用2小时后服用，每次服用后有≥7天的洗脱期。
主要参数为在有无抗酸剂情况下，瑞舒伐他汀血浆浓度-时间曲线从0至最后可定量浓度的曲线下面积（AUC(0-t)）以及观察到的瑞舒伐他汀血浆最大浓度（C(max)）。
瑞舒伐他汀与抗酸剂同时给药时，抗酸剂使瑞舒伐他汀的AUC(0-t)降低了54%（治疗的90%置信区间[CI]为0.40 - 0.53），C(max)降低了50%（90% CI 0.41 - 0.60）。当抗酸剂在瑞舒伐他汀服用2小时后给药时，抗酸剂使瑞舒伐他汀的AUC(0-t)降低了22%（90% CI 0.68 - 0.90），C(max)降低了16%（90% CI 0.70 - 1.01）。未研究重复给予抗酸剂的影响，且不能排除这可能导致比此处观察到的更强的相互作用。
瑞舒伐他汀与抗酸剂同时给药导致瑞舒伐他汀全身暴露量降低约50%。当抗酸剂在瑞舒伐他汀服用2小时后给药时，这种影响会减轻。
