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: UMLS:C0406810 (
NAME
)
13,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Carboxylesterases (CESs) located in the intestine play an unique role in the absorption of many drugs especially ester prodrugs. In order to determine the expression and hydrolyzing activity of CESs isozymes (
CES1
and CES2) located in rat intestine, the activities of
CES1
and CES2 were evaluated by the intestinal S9 incubation with imidapril and irinotecan (CPT-11), the substrates of
CES1
and CES2, respectively. The distribution characteristics of
CES1
, CES2, Pregnane X Receptor (PXR) and Constitutive Androstane Receptor were analyzed by real-time polymerase chain reaction (RT-PCR) or Western blot. Imidaprilat metabolized from imidapril by
CES1
was too low to be detected in rat intestinal S9 fractions, while there was little and even no expression of
CES1
mRNA in intestinal segments. In contrast, Vmax values for CPT-11 diminished gradually from proximal to distal segments within the rat intestine which was consistent with the mRNA expression level of CES2. These results indicated that CES2 represents the major CESs isoform in the rat complete intestine and decreased from duodenum to colon, whereas the expression of
CES1
was too low to influence the metabolism of ester prodrugs. The expression of PXR and
CAR
decreased slightly along the entire intestine on both mRNA and protein levels which indicated that PXR and
CAR
may be one of the major factors which contribute to the expression of
CES1
and CES2. Thus, the knowledge about the characteristic and site-specific expression of
CES1
and CES2 in rat intestine will help to predict the oral bioavailability of ester prodrugs.
...
PMID:Identification of carboxylesterases expressed in rat intestine and effects of their hydrolyzing activity in predicting first-pass metabolism of ester prodrugs. 2220 36
Rifampin (RF) is metabolized in the liver into an active metabolite 25-desacetylrifampin and excreted almost equally via biliary and renal routes. Various influx and efflux transporters influence RF disposition during hepatic uptake and biliary excretion. Evidence has also shown that Vitamin D deficiency (VDD) and Vitamin D receptor (VDR) polymorphisms are associated with tuberculosis (TB). Hence, genetic polymorphisms of metabolizing enzymes, drug transporters and/or their transcriptional regulators and VDR and its pathway regulators may affect the pharmacokinetics of RF. In this narrative review, we aim to identify literature that has explored the influence of single nucleotide polymorphisms (SNPs) of genes encoding drug transporters and their transcriptional regulators (SLCO1B1, ABCB1, PXR and
CAR
), metabolizing enzymes (
CES1
, CES2 and AADAC) and VDR and its pathway regulators (VDR, CYP27B1 and CYP24A1) on plasma RF concentrations in TB patients on antitubercular therapy. Available reports to date have shown that there is a lack of any association of
ABCB1
,
PXR
,
CAR
,
CES1
and
AADAC
genetic variants with plasma concentrations of RF. Further evidence is required from a more comprehensive exploration of the association of
SLCO1B1
,
CES2
and Vitamin D pathway gene variants with RF pharmacokinetics in distinct ethnic groups and a larger population to reach conclusive information.
...
PMID:Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients. 3252 34
