An Integrative Approach for Identifying a Metabolic Phenotype Predictive of Individualized Pharmacokinetics of Tacrolimus

Title
An Integrative Approach for Identifying a Metabolic Phenotype Predictive of Individualized Pharmacokinetics of Tacrolimus
Author(s)
임미선Phapale PB[Phapale PB]Kim SD[Kim SD]Lee HW[Lee HW]Kale DD[Kale DD]Kim YL[Kim YL]Cho JH[Cho JH]Hwang D[Hwang D]Yoon YR[Yoon YR]
Keywords
PERSONALIZED MEDICINE; MASS-SPECTROMETRY; SYSTEMS BIOLOGY; DRUG TOXICITY; CLINICAL-TRIALS; URINE; MODEL; MS; CLASSIFICATION; METABONOMICS
Issue Date
201004
Publisher
NATURE PUBLISHING GROUP
Citation
CLINICAL PHARMACOLOGY & THERAPEUTICS, v.87, no.4, pp.426 - 436
Abstract
Individual variation in drug response is influenced by both genes and environment. We evaluated the potential of a metabolic phenotype to predict individual variation in the pharmacokinetics (PK) of tacrolimus. Liquid chromatography-mass spectroscopy (LC-MS)-based metabolic profiling was performed on 29 healthy volunteers by measuring the levels of 1,256 metabolite ions in their predose urine samples. After oral administration of tacrolimus, we monitored its plasma concentrations in these volunteers for up to 72 h and calculated the pharmacokinetic parameters. Partial least-squares (PLS) modeling was conducted with data relating to predose urine metabolites to predict the pharmacokinetic parameters of tacrolimus and to select the metabolites that substantially contributed to such prediction. The selection of these metabolites allowed us to understand their functional role and generate a clinically applicable index to predict individualized PK of tacrolimus. In conclusion, this integrative pharmacometabolomic approach, combining the metabolic profiling of predose urine with PLS modeling, can serve as a useful tool in "individualized drug therapy."
URI
http://hdl.handle.net/YU.REPOSITORY/22649http://dx.doi.org/10.1038/clpt.2009.296
ISSN
0009-9236
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약학대학 > 약학부 > Articles
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