Key result
Non-concurrent dosing of simvastatin and amlodipine reduces simvastatin acid Cmax ~37% vs concurrent dosing.
Why the study?
The study was motivated by the need to determine if non-concurrent dosing of amlodipine and simvastatin reduces pharmacokinetic drug interactions in patients with hypertension and hyperlipidemia.
Does non-concurrent dosing of amlodipine and simvastatin reduce pharmacokinetic drug interactions compared to concurrent dosing in patients with hypertension and hyperlipidemia?
RCT (n=17)
Randomized
Does non-concurrent dosing of amlodipine and simvastatin reduce pharmacokinetic drug interactions compared to concurrent dosing in patients with hypertension and hyperlipidemia?
Absolute Event Rate: 1.2% vs 1.9%
Non-concurrent dosing of amlodipine and simvastatin significantly reduces systemic exposure to simvastatin acid compared to concurrent dosing, potentially mitigating drug interaction risks while maintaining efficacy.
Supports non-concurrent dosing to mitigate interaction risk in co-prescribed patients; confirms pharmacokinetic benefit in RCT.
OBJECTIVES: To explore if non-concurrent amlodipine dosing results in less drug interaction, the pharmacokinetic profiles, safety and efficacy endpoints were assessed following repeated doses of simvastatin, co-administered concurrently or non-concurrently with amlodipine in patients with coexisting hypertension and hyperlipidemia. METHODS: Seventeen patients randomly received daily doses of 20 mg simvastatin and 5 mg amlodipine for 6 weeks, either with both drugs at 7:00 PM (concurrent) or with simvastatin at 7:00 PM followed by amlodipine at 11:00 PM (non-concurrent). The maximum plasma concentration (Cmax) and the area under the concentration-time curve up to the last quantifiable concentration (AUClast) were estimated at steady state. Lipid profiles and blood pressure values were also compared between the concurrent and non-concurrent groups. RESULTS: The Cmax and AUClast and of simvastatin acid in the non-concurrent amlodipine dosing group were 63.2% and 66.0%, respectively, of the values obtained in the concurrent group (1.2 +/- 1.0 vs. 1.9 +/- 0.9 ng/ml and 10.3 +/- 8.3 vs. 15.6 +/- 7.5 h ng/ml, respectively, mean +/- standard deviation). Changes from baseline in lipid profile and blood pressure were comparable between the groups. CONCLUSIONS: Non-concurrent dosing may be a useful and safe therapeutic option for patients who require two or more drugs administered concomitantly, but who are likely to develop unwanted drug interactions.
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Park et al. (2010) conducted an RCT in coexisting hypertension and hyperlipidemia (n=17). Non-concurrent dosing of simvastatin and amlodipine vs. Concurrent dosing (both drugs at 7:00 PM) was evaluated on Cmax of simvastatin acid (ng/ml). Non-concurrent dosing of simvastatin and amlodipine reduced the Cmax of simvastatin acid compared to concurrent dosing (1.2 vs 1.9 ng/ml), attenuating their pharmacokinetic interaction.
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