title: A Pharmacometabonomic Approach To Predicting Metabolic Phenotypes and Pharmacokinetic Parameters of Atorvastatin in Healthy Volunteers.
abstract: Genetic polymorphism and environment each influence individual variability in drug metabolism and disposition. It is preferable to predict such variability, which may affect drug efficacy and toxicity, before drug administration. We examined individual differences in the pharmacokinetics of atorvastatin by applying gas chromatography-mass spectrometry-based metabolic profiling to predose plasma samples from 48 healthy volunteers. We determined the level of atorvastatin in plasma using liquid chromatography-tandem mass spectrometry. With the endogenous molecules, which showed a good correlation with pharmacokinetic parameters, a refined partial least-squares model was calculated based on predose data from a training set of 36 individuals and exhibited good predictive capability for the other 12 individuals in the prediction set. In addition, the model was successfully used to predictively classify individual pharmacokinetic responses into subgroups. Metabolites such as tryptophan, alanine, arachidonic acid, 2-hydroxybutyric acid, cholesterol, and isoleucine were indicated as candidate markers for predicting by showing better predictive capability for explaining individual differences than a conventional physiological index. These results suggest that a pharmacometabonomic approach offers the potential to predict individual differences in pharmacokinetics and therefore to facilitate individualized drug therapy.
authors.affiliation: China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Institute for Food and Drug Control, Nanjing 210008, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Huang
authors.affiliation: China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jiye
authors.initials: J
authors.lastname: Aa
authors.affiliation: China Pharmaceutical University, Nanjing 210009, China.|Department of Pharmacology, Jinling Hospital, Medical School of Nanjing University , Nanjing 210002, China.
authors.forename: Huning
authors.initials: H
authors.lastname: Jia
authors.affiliation: China Pharmaceutical University, Nanjing 210009, China.|Department of Pharmacology, Jinling Hospital, Medical School of Nanjing University , Nanjing 210002, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Xin
authors.affiliation: Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Tao
authors.affiliation: Clinical Pharmacology Research Laboratory, The First Affiliated Hospital of Soochow University , Suzhou 215006, China.
authors.forename: Linsheng
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Jinling Hospital, Medical School of Nanjing University , Nanjing 210002, China.
authors.forename: Bingjie
authors.initials: B
authors.lastname: Zou
authors.affiliation: China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Qinxin
authors.initials: Q
authors.lastname: Song
authors.affiliation: China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.affiliation: China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Cao
authors.affiliation: The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Yong
authors.affiliation: China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Jinling Hospital, Medical School of Nanjing University , Nanjing 210002, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000328:Adult; D019540:Area Under Curve; D000069059:Atorvastatin / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D055432:Metabolomics / Q000379:methods*; D057285:Precision Medicine; D055815:Young Adult
chemical_list: D000069059:Atorvastatin
keywords: atorvastatin; metabolomics; personalized medicine; pharmacokinetics; pharmacometabonomics; precision medicine; prediction