PMID- 36993275
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240212
DP  - 2023 Mar 14
TI  - 2-Deoxyglucose and hydroxychloroquine HPLC-MS-MS analytical methods and 
      pharmacokinetic interactions after oral co-administration in male rats.
LID - rs.3.rs-2675386 [pii]
LID - 10.21203/rs.3.rs-2675386/v1 [doi]
AB  - Our previous work has shown a synergistic tumoricidal action of the hexokinase 
      (HK) inhibitor 2-deoxyglucose (2-DG) and the autophagy inhibitor chloroquine (CQ) 
      on HK2-addicted prostate cancers in animal models through intraperitoneal 
      injections. Here we developed high performance liquid chromatography-tandem mass 
      spectrometry (HPLC-MS-MS) methods for 2-DG and clinically favored drug 
      hydroxychloroquine (HCQ) and explored PK interaction of the orally administered 
      drugs in a jugular vein cannulated male rat model, which allowed serial blood 
      collection before and 0.5, 1, 2, 4 and 8 h after a single gavage dose of each 
      drug alone or simultaneously after appropriate washout periods between the drugs. 
      The results demonstrated a rapid and satisfactory separation of 2-DG standard 
      from common monosaccharides by HPLC-MS-MS multi-reaction monitoring (MRM) and the 
      presence of endogenous "2-DG". Application of the HPLC-MS-MS 2-DG and HCQ methods 
      to sera samples of 9 evaluable rats showed a peak time (T(max)) of 2-DG of 0.5 h 
      after 2-DG dosing alone or with HCQ and glucose-like PK behavior. With a 
      seemingly bi-modal time course for HCQ, the T(max) for HCQ dosing alone (1.2 h) 
      was faster than that for the combination (2 h; p = 0.013, 2-tailed t-test). After 
      combination dosing, the peak concentration (C(max)) and area under the curve 
      (AUC) of 2-DG were decreased by 54% (p < 0.0001) and 52%, whereas those for HCQ 
      were decreased by 40% (p = 0.026) and 35%, respectively, compared to single 
      dosing. The data suggest significant negative PK interactions between the two 
      oral drugs taken simultaneously and warrant optimization efforts for the 
      combination regimen.
FAU - Sun, Dongxiao
AU  - Sun D
AD  - Penn State College of Medicine.
FAU - Kim, Sangyub
AU  - Kim S
AD  - Penn State College of Medicine.
FAU - Karelia, Deepkamal
AU  - Karelia D
AD  - Penn State College of Medicine.
FAU - Deng, Yibin
AU  - Deng Y
AD  - University of Minnesota.
FAU - Jiang, Cheng
AU  - Jiang C
AD  - Penn State College of Medicine.
FAU - Lu, Junxuan
AU  - Lu J
AD  - Penn State College of Medicine.
LA  - eng
GR  - R21 CA218774/CA/NCI NIH HHS/United States
PT  - Preprint
DEP - 20230314
PL  - United States
TA  - Res Sq
JT  - Research square
JID - 101768035
UIN - Pharmacol Res Perspect. 2024 Feb;12(1):e1173. PMID: 38294142
PMC - PMC10055671
OTO - NOTNLM
OT  - 2-deoxyglucose
OT  - HPLC-MS-MS
OT  - drug-drug interaction
OT  - hydroxychloroquine
OT  - oral drug-drug PK interference
EDAT- 2023/03/31 06:00
MHDA- 2023/03/31 06:01
PMCR- 2023/03/29
CRDT- 2023/03/30 02:51
PHST- 2023/03/31 06:00 [pubmed]
PHST- 2023/03/31 06:01 [medline]
PHST- 2023/03/30 02:51 [entrez]
PHST- 2023/03/29 00:00 [pmc-release]
AID - rs.3.rs-2675386 [pii]
AID - 10.21203/rs.3.rs-2675386/v1 [doi]
PST - epublish
SO  - Res Sq [Preprint]. 2023 Mar 14:rs.3.rs-2675386. doi: 10.21203/rs.3.rs-2675386/v1.