Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Fexofenadine hydrochloride
(
FEX
), a second generation H(1)-receptor antagonist, is mainly eliminated from the liver into bile in unchanged form. Recent studies have shown that
FEX
can be accepted by human MDR1 (
P-glycoprotein
), OATP1A2 [organic anion-transporting polypeptide (OATP)-A, and OATP2B1 (OATP-B)] expression systems. However, other transporters responsible for the hepatic uptake of
FEX
have not yet been identified. In the present study, we evaluated the contribution of OATP family transporters, namely OATP1B1 (OATP2/OATP-C), OATP1B3 (OATP8), and OATP2B1 (OATP-B), to
FEX
uptake using transporter-expressing HEK293 (human embryonic kidney) cells. The uptake of
FEX
in OATP1B3-expressing cells was significantly greater than that in vector-transfected cells. On the other hand, OATP1B1- or OATP2B1-mediated uptake of
FEX
was not statistically significant. OATP1B3-mediated transport could be explained by a one-saturable component with a Michaelis constant (K(m)) of 108 +/- 11 microM. The inhibitory effect of
FEX
on the uptake of estrone-3-sulfate (E(1)S), cholecystokinin octapeptide (CCK-8), and 17beta-estradiol-17beta-d-glucuronide (E(2)17betaG) was also examined. Both OATP1B1- and OATP1B3-mediated E(2)17betaG uptake was inhibited by
FEX
. The K(i) values were 148 +/- 61 and 205 +/- 72 microM for OATP1B1 and OATP1B3, respectively.
FEX
also inhibited OATP1B3-mediated CCK-8 uptake and OATP1B1-mediated E(1)S uptake with a K(i) value of 83.3 +/- 15.3 and 257 +/- 84 microM, respectively, suggesting that
FEX
could not be used as a specific inhibitor for OATP1B1 and OATP1B3, although
FEX
was preferentially accepted by OATP1B3. In conclusion, this is, to our knowledge, the first demonstration that OATP1B3 is thought to be a major transporter involved in hepatic uptake of
FEX
in humans.
...
PMID:Contribution of OATP (organic anion-transporting polypeptide) family transporters to the hepatic uptake of fexofenadine in humans. 1601 68
