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OBJECTIVE To investigate the pharmacogenetic effect of SLCO1B1 *1a, *1b, *5 and *15 polymorphisms on irinotecan disposition in Asian cancer patients. EXPERIMENTAL DESIGN Irinotecan was administered over 90 min either at 100 mg/m on days 1, 8 and 15 with the regimen being repeated every 28 days (N=28) or at 375 mg/m once every three weeks (N=43). Plasma(More)
The influence of three high frequency ABCB1 polymorphisms (c.1236C>T, c.2677G>A/T, and c.3435C>T) and the ABCG2 c.421C>A polymorphism on the disposition of doxorubicin in Asian breast cancer patients receiving adjuvant chemotherapy was investigated in the present study. The allelic frequency of the ABCB1 c.1236T, c.2677T, c.2677A, and c.3435T variants were(More)
OBJECTIVE To identify novel polymorphisms in the solute carrier SLC22A16 gene and determine their influence on the pharmacokinetics of doxorubicin and doxorubicinol in Asian breast cancer patients. METHODS SLC22A16 coding regions were screened in a total of 400 healthy subjects belonging to three distinct Asian ethnic groups (Chinese [n = 100], Malays [n(More)
BACKGROUND AND OBJECTIVE Organic anion transporting polypeptide 1B1 (OATP1B1, encoded by SLCO1B1) is a sinusoidal influx transporter of human hepatocytes. Our aim was to characterize the role of OATP1B1 in the hepatic uptake of bile acids in vivo. METHODS Fasting blood samples were drawn from 24 healthy volunteers with SLCO1B1 c.388AA-c.521TT (*1A/*1A)(More)
  • Guo Ma, Jiayuan Lin, +4 authors Peng Zhang
  • 2014
Bilirubin, an important endogenous substances and liver function index in humans, is primarily eliminated via UGT1A1-catalyzed glucuronidation. Instability of bilirubin and its glucuronides brings substantial technical challenges to conduct in vitro bilirubin glucuronidation assay. In the present study, we developed a simple and robust HPLC method for(More)
We report a sensitive and robust method to determine cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), and their taurine- and glycine-conjugate concentrations in human plasma using liquid chromatography-tandem mass spectrometry. Activated charcoal was utilized to prepare bile(More)
Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme of bile acid production in human beings, and organic anion-transporting polypeptide 1B1 (OATP1B1) may influence bile acid hepatic uptake and cholesterol and bile acid synthesis rate. Our purpose was to investigate the effects of gender and CYP7A1 and SLCO1B1 polymorphisms on the fasting plasma(More)
Warfarin is a widely prescribed anticoagulant for thromboembolic disorders and exhibits wide inter-individual differences in its pharmacodynamic effects. Warfarin exerts its anticoagulant effect by inhibiting the enzymatic activity of vitamin K 2,3-epoxide reductase complex, subunit 1 (VKORC1) which regenerates reduced vitamin K as an essential cofactor for(More)
SUMMARY Warfarin-induced bleeding complications and high inter-patient variability are major hindrances to oral anticoagulant therapy. The present study identifies the influence of VKORC1 diplotypes, CYP2C9 and CYP2C19 variants on warfarin disposition and dose requirements in Chinese patients (n=107). The study subjects were genotyped for VKORC1, CYP2C9 and(More)
To investigate possible effects of the SLCO1B1 polymorphism on the pharmacokinetics of ursodeoxycholic acid (UDCA) and its metabolites in healthy volunteers. In a crossover study with two phases, 15 healthy volunteers with the SLCO1B1*1A/*1A genotype, seven with the *1B/*1B genotype, and five with the *15/*15 or *5/*15 genotype ingested placebo or a single(More)