-transparent.png){kind=logo}
Terfenadine (Seldane) undergoes extensive metabolism to form azacyclonol and terfenadine alcohol. Terfenadine alcohol is subsequently metabolized to azacyclonol and terfenadine acid. Although testosterone 6 beta-hydroxylation [CYP3A(4)] has been shown to be the principal enzyme involved in the first step in terfenadine's biotransformation (formation of azacyclonol and terfenadine alcohol), the enzymes catalyzing the subsequent metabolic steps in the conversion of terfenadine alcohol to azacyclonol and terfenadine acid have not been identified. The purpose of these studies was to determine the role of cytochrome P450 isoforms in the biotransformation of terfenadine and terfenadine alcohol. To this end, both terfenadine and its alcohol were incubated with 10 individual human liver microsomal samples that have been characterized for major isozyme activities. The metabolites and parent drugs were quantified by HPLC. The formation of azacyclonol and terfenadine alcohol from terfenadine is confirmed to be catalyzed predominantly by CYP3A(4) isozyme, and the ratio of the rate of terfenadine alcohol formation to that of azacyclonol is 3:1. Involvement of the CYP3A(4) in terfenadine metabolism was further confirmed by the following studies: a) inhibition of terfenadine alcohol formation by ketoconazole and troleandomycin, two specific inhibitors of CYP3A(4), and b) time course of terfenadine alcohol formation by cloned human CYP3A(4). When terfenadine alcohol was used as substrate, both the terfenadine acid and azacyclonol formation were also catalyzed by CYP3A(4) isozyme. However, the rate of formation of the terfenadine acid metabolite is almost 9 times faster than that of azacyclonol. The net ratio of terfenadine acid to azacyclonol is 2:1.
K H Ling, and
G A Leeson, and
S D Burmaster, and
R H Hook, and
M K Reith, and
L K Cheng
August 2021,
Xenobiotica; the fate of foreign compounds in biological systems,
K H Ling, and
G A Leeson, and
S D Burmaster, and
R H Hook, and
M K Reith, and
L K Cheng
April 1997,
Biochemical pharmacology,
K H Ling, and
G A Leeson, and
S D Burmaster, and
R H Hook, and
M K Reith, and
L K Cheng
February 2000,
Life sciences,
K H Ling, and
G A Leeson, and
S D Burmaster, and
R H Hook, and
M K Reith, and
L K Cheng
January 1998,
Toxicology letters,
K H Ling, and
G A Leeson, and
S D Burmaster, and
R H Hook, and
M K Reith, and
L K Cheng
May 2012,
Xenobiotica; the fate of foreign compounds in biological systems,
K H Ling, and
G A Leeson, and
S D Burmaster, and
R H Hook, and
M K Reith, and
L K Cheng
June 1991,
Toxicology and applied pharmacology,
K H Ling, and
G A Leeson, and
S D Burmaster, and
R H Hook, and
M K Reith, and
L K Cheng
December 1997,
Research communications in molecular pathology and pharmacology,
K H Ling, and
G A Leeson, and
S D Burmaster, and
R H Hook, and
M K Reith, and
L K Cheng
April 1999,
Cancer research,
K H Ling, and
G A Leeson, and
S D Burmaster, and
R H Hook, and
M K Reith, and
L K Cheng
December 1995,
Cell biology and toxicology,
K H Ling, and
G A Leeson, and
S D Burmaster, and
R H Hook, and
M K Reith, and
L K Cheng
April 2004,
Drug metabolism and disposition: the biological fate of chemicals,
