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.


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 > or = 7 days between each.


METHODS
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.
Martin
Paul D
PD
AstraZeneca, Alderley Park, Cheshire, UK. paul.martin@astrazeneca.com
Schneck
Dennis W
DW
Dane
Aaron L
AL
Warwick
Michael J
MJ
D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000009:adverse effects*; D000863:Antacids / Q000008:administration & dosage / Q000009:adverse effects*; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics; D008276:Magnesium Hydroxide / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors
D000863:Antacids; D000924:Anticholesteremic Agents; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000536:Aluminum Hydroxide; D000068718:Rosuvastatin Calcium; D008276:Magnesium Hydroxide