The effect of a combination antacid preparation containing aluminium hydroxide and magnesium hydroxide on rosuvastatin pharmacokinetics

Objective: 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. Research design and methods: 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 7 days between each. Main outcome measures: 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. Results: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. Conclusions: 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.