AIM: Selected bile acids (BAs) in plasma have been proposed as endogenous probes for assessing drug-drug interactions involving hepatic drug transporters such as the organic anion-transporting polypeptides (OATP1B1 and OATP1B3). MATERIALS & METHODS: Plasma extracts were analyzed for selected BAs using a triple TOF API6600 high-resolution mass spectrometer. RESULTS: Glycodeoxycholic acid 3-sulfate, glycochenodeoxycholic acid 3-sulfate, glycodeoxycholic acid 3-O-β-glucuronide and glycochenodeoxycholic acid 3-O-β-glucuronide are presented as potential OATP1B1/3 biomarkers. CONCLUSION: Six BAs are quantified in human plasma using a multiplexed high-resolution mass spectrometry method. Glycodeoxycholic acid 3-sulfate and glycodeoxycholic acid 3-O-β-glucuronide are proposed as potential biomarkers based on observed four- to fivefold increase in plasma AUC (vs placebo), following administration of a compound known to present as an OATP1B1/3 inhibitor in vitro.
AIM: Selected bile acids (BAs) in plasma have been proposed as endogenous probes for assessing drug-drug interactions involving hepatic drug transporters such as the organic anion-transporting polypeptides (OATP1B1 and OATP1B3). MATERIALS & METHODS: Plasma extracts were analyzed for selected BAs using a triple TOF API6600 high-resolution mass spectrometer. RESULTS:Glycodeoxycholic acid 3-sulfate, glycochenodeoxycholic acid 3-sulfate, glycodeoxycholic acid 3-O-β-glucuronide and glycochenodeoxycholic acid 3-O-β-glucuronide are presented as potential OATP1B1/3 biomarkers. CONCLUSION: Six BAs are quantified in human plasma using a multiplexed high-resolution mass spectrometry method. Glycodeoxycholic acid 3-sulfate and glycodeoxycholic acid 3-O-β-glucuronide are proposed as potential biomarkers based on observed four- to fivefold increase in plasma AUC (vs placebo), following administration of a compound known to present as an OATP1B1/3 inhibitor in vitro.
Entities:
Keywords:
HRMS; bile acids; biomarkers; organic anion-transporting polypeptide
Authors: Mikko Neuvonen; Päivi Hirvensalo; Aleksi Tornio; Brian Rago; Mark West; Sarah Lazzaro; Sumathy Mathialagan; Manthena Varma; Matthew A Cerny; Chester Costales; Ragu Ramanathan; A David Rodrigues; Mikko Niemi Journal: Clin Pharmacol Ther Date: 2020-10-18 Impact factor: 6.875