title: Drug interaction between oral atorvastatin and verapamil in healthy subjects: effects of atorvastatin on the pharmacokinetics of verapamil and norverapamil.
abstract: OBJECTIVE
  It has been reported that verapamil and atorvastatin are inhibitors of both P-glycoprotein (P-gp) and microsomal cytochrome P450 (CYP) 3A4, and verapamil is a substrate of both P-gp and CYP3A4. Thus, it could be expected that atorvastatin would alter the absorption and metabolism of verapamil.
  
  
  METHODS
  The pharmacokinetic parameters of verapamil and one of its metabolites, norverapamil, were compared after oral administration of verapamil (60 mg) in the presence or absence of oral atorvastatin (40 mg) in 12 healthy volunteers.
  
  
  RESULTS
  Pharmacokinetics of verapamil were significantly altered by the coadministration of atorvastatin compared with those of without atorvastatin. For example, the total area under the plasma-concentration time curve to the last measured time, 24 h, in plasma (AUC(0-24) (h)) of verapamil increased significantly by 42.8%. Thus, the relative bioavailability increased by the same magnitude with atorvastatin. Although the AUC(0-24) (h) of norverapamil was not significantly different between two groups of humans, the AUC(0-24) (h, norverapamil)/ AUC(0-24) (h, verapamil) ratio was significantly reduced (27.5% decrease) with atorvastatin.
  
  
  CONCLUSIONS
  The above data suggest that atorvastatin could inhibit the absorption of verapamil via inhibition of P-gp and/or the metabolism of verapamil by CYP3A4 in humans.
authors.affiliation: College of Medicine, Chosun University, 375, Su-suk Dong, Dong-Gu, Gwangju, 501-759, South Korea.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Choi
authors.forename: Wan-Gyun
authors.initials: WG
authors.lastname: Shin
authors.forename: Jun-Shik
authors.initials: JS
authors.lastname: Choi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D019540:Area Under Curve; D000069059:Atorvastatin; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000097:blood / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011758:Pyrroles / Q000494:pharmacology*; D014700:Verapamil / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000924:Anticholesteremic Agents; D002121:Calcium Channel Blockers; D006538:Heptanoic Acids; D011758:Pyrroles; C016904:norverapamil; D000069059:Atorvastatin; D014700:Verapamil; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human