2 ‐Deoxyglucose and hydroxychloroquine HPLC‐MS–MS analytical methods and pharmacokinetic interactions after oral co‐administration in male rats

Serum concentration versus time curves after single dose alone or combination dosing. (A) 2-DG; (B) HCQ. AbstractOur previous work has shown a synergistic tumoricidal efficacy of combining the hexokinase (HK) inhibitor 2-deoxyglucose (2-DG) and the autophagy inhibitor chloroquine (CQ) through intraperitoneal injections on HK2-addicted prostate cancers in animal models. The pharmacokinetic (PK) behaviors of these oral drugs after simultaneous oral administration have not been reported. We developed high-performance liquid chromatography –tandem mass spectrometry (HPLC-MS–MS) analytical methods for 2-DG and the clinically favored drug hydroxychloroquine (HCQ) for sera samples. Using a jugular vein-cannulated male rat model with serial blood collection before and after a single gavage dose of each drug alone or in combination, we examined their PK metrics for drug–drug interactions. The data demonstrated a rapid and complete separation of 2-DG from common monosaccharides by HPLC-MS–MS multi-reaction monitoring. Application of the HPLC-MS–MS 2-DG and HCQ methods to sera samples of nine rats showed a peak time (Tmax) for 2-DG of 0.5  h after 2-DG alone or with HCQ and identical post-peak half-life of approximately 1 h. With a seemingly bi-modal time course for HCQ, theTmax for HCQ alone (1.2  h) was faster than that for the combination (2 h;p = .017). After combination dosing, the peak concentration (Cmax) and area under the curve (AUC0-4h) of 2-DG were decre...
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: SHORT REPORT Source Type: research