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The dietary polyphenol trans-resveratrol (3,5,4'-trihydroxy-trans-stilbene) is glucuronidated at the 3 and 4' positions to yield two major glucuronide conjugates, resveratrol-3-O-glucuronide (R3G) and resveratrol-4'-O-glucuronide (R4'G). The major enzymes catalyzing this conjugation reaction are members of the UDP-glucuronosyl transferase (UGT) 1A family(More)
BACKGROUND A barrier to statin therapy is myopathy associated with elevated systemic drug exposure. Our objective was to examine the association between clinical and pharmacogenetic variables and statin concentrations in patients. METHODS AND RESULTS In total, 299 patients taking atorvastatin or rosuvastatin were prospectively recruited at an outpatient(More)
The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes genotype-based drug guidelines to help clinicians understand how available genetic test results could be used to optimize drug therapy. CPIC has focused initially on well-known examples of pharmacogenomic associations that have been implemented in selected clinical settings, publishing(More)
The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin. Resultant indirect hyperbilirubinemia with jaundice can cause premature discontinuation of atazanavir. Risk for bilirubin-related discontinuation is highest among(More)
The dietary polyphenol resveratrol (RES) exists as cis- and trans-isomers with known stereospecific and stereoselective glucuronidation at the 3 and 4' positions by distinct UGT1A isoforms. We examined cis-RES glucuronidation in various protein sources. UGT1A6 or UGT1A1 genotype-dependent cis-or trans-RES glucuronidation, respectively, was further(More)
Trans-3,5,4'-trihydroxystilbene (trans-resveratrol, RES) exhibits very low bioavailability due to extensive conjugative metabolism. Whether RES metabolites exhibit pharmacologic activity is of great interest. The present study aimed at synthesis of monoconjugates of RES - the 3- and 4' monosulfates (R3S and R4'S), and the 3- and 4' monoglucuronides (R3G and(More)
Efforts to define the genetic architecture underlying variable statin response have met with limited success, possibly because previous studies were limited to effect based on a single dose. We leveraged electronic medical records (EMRs) to extract potency (ED50) and efficacy (Emax) of statin dose-response curves and tested them for association with 144(More)
Metabolites in safety testing have gained a lot of attention recently. Regulatory agencies have suggested that the kinetics of preformed and in vivo-formed metabolites are comparable. This subject has been a topic of debate. We have compared the kinetics of in vivo-formed with preformed metabolites. trans-3,5,4'-Trihydroxystilbene [trans-resveratrol (RES)](More)
AIMS The only FDA approved medication for colorectal cancer (CRC) prevention is celecoxib. Its adverse effects underline the need for safer drugs. Polyphenols like resveratrol are in clinical trials for this purpose. This study aimed at examining effects of resveratrol alone and in combination with curcumin or chrysin on UGT induction in Caco-2 cells.(More)
BACKGROUND The uridine diphosphoglucuronosyltransferase (UGT) superfamily of enzymes catalyzes conjugative metabolism of numerous endobiotics and xenobiotics. Pharmacogenetic variation has been reported in almost all UGT family members. OBJECTIVE To discuss tools available for evaluation of UGT polymorphisms. METHODS Literature search was done to(More)