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The effect of the newly developed angiotensin receptor II antagonist fimasartan on the pharmacokinetics of atorvastatin in relation to OATP1B1 in healthy male volunteers

Authors
 Shin, Kwang-Hee  ;  Kim, Tae-Eun  ;  Kim, Sung Eun  ;  Lee, Min Goo  ;  Song, Im-Sook  ;  Yoon, Seo Hyun  ;  Cho, Joo-Youn  ;  Jang, In-Jin  ;  Shin, Sang-Goo  ;  Yu, Kyung-Sang 
Citation
 JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, Vol.58(5) : 492-499, 2011 
Journal Title
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
ISSN
 0160-2446 
Issue Date
2011
MeSH
Adult ; Angiotensin II Type 1 Receptor Blockers/pharmacology* ; Area Under Curve ; Atorvastatin Calcium ; Biphenyl Compounds/pharmacology* ; Cross-Over Studies ; Drug Interactions/physiology ; Estrone/analogs & derivatives ; Estrone/metabolism ; Heptanoic Acids/adverse effects ; Heptanoic Acids/blood ; Heptanoic Acids/metabolism ; Heptanoic Acids/pharmacokinetics* ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/blood ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/metabolism ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics ; Male ; Organic Anion Transporters/drug effects* ; Organic Anion Transporters/genetics ; Organic Anion Transporters/metabolism ; Pyrimidines/pharmacology* ; Pyrroles/adverse effects ; Pyrroles/blood ; Pyrroles/metabolism ; Pyrroles/pharmacokinetics* ; RNA, Complementary/genetics ; Solute Carrier Organic Anion Transporter Family Member 1b1 ; Tetrazoles/pharmacology* ; Young Adult
Keywords
fimasartan ; atorvastatin ; pharmacokinetics ; drug interaction ; OATP1B1
Abstract
OBJECTIVE: Interactions between coadministered drugs may unfavorably affect pharmacokinetics. This study evaluated whether fimasartan, an angiotensin receptor II antagonist, affected the pharmacokinetics of atorvastatin.

METHODS: A randomized, open-label, 2-period, 2-sequence, crossover, multiple-dosing study was conducted with 24 healthy male volunteers. Twelve subjects received 80-mg atorvastatin once daily for 7 days; later, they received 80-mg atorvastatin with 240-mg fimasartan for 7 days. Twelve other subjects received the same drugs in the opposite sequence. Blood samples were collected scheduled intervals for 24 hours after the last dosing to determine plasma concentrations of atorvastatin acid, atorvastatin lactone, 2-hydroxy atorvastatin acid, and 2-hydroxy atorvastatin lactone.

RESULTS: Compared with atorvastatin alone, coadministration of fimasartan and atorvastatin increased the atorvastatin acid mean (95% confidence interval) maximum concentration (Cmax,ss) by 1.89-fold (1.49-2.39) and the area under the concentration curve (AUCτ,ss) by 1.19-fold (0.96-1.48). Fimasartan also increased the mean 2-hydroxy atorvastatin acid Cmax,ss and AUCτ,ss by 2.45-fold (1.80-3.35) and 1.42-fold (1.09-1.85), respectively. The Cmax,ss and AUCτ,ss of the lactone forms of atorvastatin showed smaller changes than those observed for the acidic forms.

CONCLUSION: We showed that fimasartan raised plasma atorvastatin concentrations. In vitro tests suggested that this effect may have been mediated by fimasartan inhibition of organic anion-transporting polypeptide 1B1.
Full Text
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=00005344-201111000-00007&LSLINK=80&D=ovft
DOI
10.1097/FJC.0b013e31822b9092
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/95251
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