title: Non-concurrent dosing attenuates the pharmacokinetic interaction between amlodipine and simvastatin.
abstract: OBJECTIVE
  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.
authors.affiliation: Cardiovascular Center, Guro Hospital, Korea University, Seoul, South Korea.
authors.forename: C G
authors.initials: CG
authors.lastname: Park
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: J W
authors.initials: JW
authors.lastname: Choi
authors.forename: S J
authors.initials: SJ
authors.lastname: Lee
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: H E
authors.initials: HE
authors.lastname: Lim
mesh_terms: D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000959:Antihypertensive Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017311:Amlodipine; D019821:Simvastatin