Pharmacometabolomics Informs About Pharmacokinetic Profile of Methylphenidate.

ABSTRACT: Carboxylesterase 1 (CES1) metabolizes methylphenidate and other drugs. CES1 gene variation only partially explains pharmacokinetic (PK) variability. Biomarkers predicting the PKs of drugs metabolized by CES1 are needed. We identified lipids in plasma from 44 healthy subjects that correlated with CES1 activity as determined by PK parameters of methylphenidate including a ceramide (q value = 0.001) and a phosphatidylcholine (q value = 0.005). Carriers of the CES1 143E allele had decreased methylphenidate metabolism and altered concentration of this phosphatidylcholine (q value = 0.040) and several high polyunsaturated fatty acid lipids (PUFAs). The half-maximal inhibitory concentration (IC₅₀ ) values of chenodeoxycholate and taurocholate were 13.55 and 19.51 μM, respectively, cons

SUBMITTER: Kaddurah-Daouk R 

PROVIDER: S-EPMC6118295 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature