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Atorvastatin does not Produce a Clinically Significant Effect on the Pharmacokinetics of Terfenadine
Author(s) -
Stern Ralph H.,
Smithers Jacquelyn A.,
Olson Stephen C.
Publication year - 1998
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1998.tb04816.x
Subject(s) - terfenadine , fexofenadine , atorvastatin , pharmacokinetics , pharmacology , grapefruit juice , cyp3a4 , medicine , drug interaction , pharmacodynamics , cmax , chemistry , cytochrome p450 , metabolism
The effect of atorvastatin, a CYP3A4 substrate, on the pharmacokinetics of terfenadine and its carboxylic acid metabolite, fexofenadine, were evaluated. Single 120‐mg doses of terfenadine were given 2 weeks apart to healthy volunteers with 80‐mg daily doses of atorvastatin administered from 7 days before through 2 days after the second terfenadine dose. Concentrations of terfenadine and fexofenadine were measured for 72 hours after each terfenadine dose. Administration of terfenadine alone or in combination with atorvastatin produced no alterations in the QTc interval. For terfenadine, atorvastatin coadministration produced an 8% decrease in maximum concentration (C max ), a 35% increase in area under the concentration‐time curve extrapolated to infinity (AUC 0‐∞ ), and a 2% decrease in elimination half‐life (t 1/2 ). For fexofenadine, atorvastatin coadministration produced a 16% decrease in C max , a 2% decrease in AUC 0‐∞ , and a 51% increase in t 1/2 . None of these changes achieved statistical significance. Coadministration of atorvastatin with terfenadine does not result in a clinically significant drug interaction. Because 80 mg is the highest atorvastatin dose used clinically, drug interactions mediated by CYP3A4 inhibition are unlikely in clinical practice.