PMID- 38294142
OWN - NLM
STAT- MEDLINE
DCOM- 20240201
LR  - 20240212
IS  - 2052-1707 (Electronic)
IS  - 2052-1707 (Linking)
VI  - 12
IP  - 1
DP  - 2024 Feb
TI  - 2-Deoxyglucose and hydroxychloroquine HPLC-MS-MS analytical methods and 
      pharmacokinetic interactions after oral co-administration in male rats.
PG  - e1173
LID - 10.1002/prp2.1173 [doi]
LID - e1173
AB  - Our 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 
      (T(max) ) 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, 
      the T(max) for HCQ alone (1.2 h) was faster than that for the combination (2 h; 
      p = .017). After combination dosing, the peak concentration (C(max) ) and area 
      under the curve (AUC(0-4h) ) of 2-DG were decreased by 53.8% (p = .0004) and 
      53.7% (p = .0001), whereas AUC(0-8h) for HCQ was decreased by 30.8% (p = .0279) 
      from the respective single dosing. Without changing the mean residence time 
      (MRT(0-infinity) ) of each drug, the combination affected the apparent volume of 
      distribution (V(d) ) and clearance (CL) of 2-DG, and CL for HCQ without affecting 
      its V(d) . We observed significant negative PK interactions, probably at the 
      intestinal absorption level, between 2-DG and HCQ taken simultaneously by mouth. 
      Future optimization efforts are warranted for their combination regimen for 
      clinical translation.
CI  - (c) 2024 The Authors. Pharmacology Research & Perspectives published by British 
      Pharmacological Society and American Society for Pharmacology and Experimental 
      Therapeutics and John Wiley & Sons Ltd.
FAU - Sun, Dongxiao
AU  - Sun D
AUID- ORCID: 0000-0003-4902-4292
AD  - Department of Pharmacology, Pennsylvania State University College of Medicine, 
      Hershey, Pennsylvania, USA.
AD  - Pennsylvania State University College of Medicine Mass Spectrometry Core 
      Facility, Hershey, Pennsylvania, USA.
FAU - Kim, Sangyub
AU  - Kim S
AUID- ORCID: 0000-0002-0190-8593
AD  - Department of Pharmacology, Pennsylvania State University College of Medicine, 
      Hershey, Pennsylvania, USA.
FAU - Karelia, Deepkamal
AU  - Karelia D
AUID- ORCID: 0000-0002-3747-394X
AD  - Department of Pharmacology, Pennsylvania State University College of Medicine, 
      Hershey, Pennsylvania, USA.
FAU - Deng, Yibin
AU  - Deng Y
AUID- ORCID: 0000-0001-5711-3565
AD  - Department of Urology, University of Minnesota College of Medicine, Minneapolis, 
      Minnesota, USA.
FAU - Jiang, Cheng
AU  - Jiang C
AUID- ORCID: 0000-0002-8735-1254
AD  - Department of Pharmacology, Pennsylvania State University College of Medicine, 
      Hershey, Pennsylvania, USA.
FAU - Lu, Junxuan
AU  - Lu J
AUID- ORCID: 0000-0002-2354-7186
AD  - Department of Pharmacology, Pennsylvania State University College of Medicine, 
      Hershey, Pennsylvania, USA.
AD  - Penn State Cancer Institute, Hershey, Pennsylvania, USA.
LA  - eng
GR  - R21 CA218774/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Pharmacol Res Perspect
JT  - Pharmacology research & perspectives
JID - 101626369
RN  - 4QWG6N8QKH (Hydroxychloroquine)
RN  - 9G2MP84A8W (Deoxyglucose)
SB  - IM
UOF - Res Sq. 2023 Mar 14;:. PMID: 36993275
MH  - Male
MH  - Rats
MH  - Animals
MH  - *Hydroxychloroquine/pharmacokinetics
MH  - Chromatography, High Pressure Liquid
MH  - *Liquid Chromatography-Mass Spectrometry
MH  - Administration, Oral
MH  - Deoxyglucose
PMC - PMC10829054
OTO - NOTNLM
OT  - 2-deoxyglucose
OT  - drug-drug interaction
OT  - hydroxychloroquine
OT  - oral drug-drug PK interference
COIS- The authors have no conflicts of interest to declare.
EDAT- 2024/01/31 12:44
MHDA- 2024/02/01 06:43
PMCR- 2024/01/31
CRDT- 2024/01/31 08:08
PHST- 2023/12/21 00:00 [revised]
PHST- 2023/09/28 00:00 [received]
PHST- 2024/01/11 00:00 [accepted]
PHST- 2024/02/01 06:43 [medline]
PHST- 2024/01/31 12:44 [pubmed]
PHST- 2024/01/31 08:08 [entrez]
PHST- 2024/01/31 00:00 [pmc-release]
AID - PRP21173 [pii]
AID - 10.1002/prp2.1173 [doi]
PST - ppublish
SO  - Pharmacol Res Perspect. 2024 Feb;12(1):e1173. doi: 10.1002/prp2.1173.