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Predicting Pharmacokinetics Variation of Faropenem Using a Pharmacometabonomic Approach
Xiaoqing Xing1,2, Pengcheng Ma3, Qing Huang4
1Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, School of Pharmacy , China Pharmaceutical University , Nanjing 210009 , China.
Journal of Proteome Research
|October 17, 2019
Summary
Individual variation in faropenem drug response was predicted using a pharmacometabonomic approach. Specific metabolites were identified as biomarkers, suggesting organic anion transporters may explain pharmacokinetic variability.
Area of Science:
- Pharmacology
- Metabolomics
- Biomarker Discovery
Background:
- Significant individual variability exists in faropenem pharmacokinetics.
- Predicting drug response is crucial for personalized medicine.
Purpose of the Study:
- To predict faropenem drug response using a pharmacometabonomic approach.
- To identify biomarkers associated with faropenem pharmacokinetics.
Main Methods:
- Metabolic profiling of 36 healthy volunteers using gas chromatography-mass spectrometry (GC/MS).
- Pharmacokinetic parameter calculation via high-performance liquid chromatography-tandem mass spectrometry (LC/MS/MS).
- Two-stage partial least squares analysis for biomarker screening and prediction.
Main Results:
- Successful prediction of area under the curve (AUC) and maximum concentration (Cmax) for faropenem.
- Identified candidate biomarkers including valine, proline, aspartic acid, gluconic acid, glucuronic acid, and 2-ketoisocaproic acid.
- Pathway enrichment analysis implicated organic anion transporters 1 (OAT1) and 3 (OAT3) in pharmacokinetic variability.
Conclusions:
- Pharmacometabonomics can effectively predict faropenem pharmacokinetics.
- Specific metabolites serve as predictive biomarkers for faropenem response.
- OAT1 and OAT3 transporters are likely contributors to individual differences in faropenem pharmacokinetics, verified in rat models.
Keywords:
faropenemmetabonomicsorganic anion transporterpersonalized medicinepharmacokineticspharmacometabonomicspredictionMore Related Videos
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