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• W2904754470 abstract "Honokiol (HK) usage is greatly restricted by its poor aqueous solubility and limited oral bioavailability. We synthesized and characterized a novel phosphate prodrug of honokiol (HKP) for in vitro and in vivo use. HKP greatly enhanced the aqueous solubility of HK (127.54 ± 15.53 mg/ml) and the stability in buffer solution was sufficient for intravenous administration. The enzymatic hydrolysis of HKP to HK was extremely rapid in vitro (T1/2= 8.9 ± 2.11 s). Pharmacokinetics studies demonstrated that after intravenous administration of HKP (32 mg/kg), HKP was converted rapidly to HK with a time to reach the maximum plasma concentration of ∼5 min. The prodrug HKP achieved an improved T1/2 (7.97 ± 1.30 h) and terminal volume of distribution (26.02 ± 6.04 ml/kg) compared with direct injection of the equimolar parent drug (0.66 ± 0.01 h) and (2.90 ± 0.342 ml/kg), respectively. Furthermore, oral administration of HKP showed rapid and improved absorption compared with the parent drug. HKP was confirmed to maintain the bioactivity of the parent drug for ameliorating ischemia-reperfusion injury by decreasing brain infarction and improving neurologic function. Taken together, HKP is a potentially useful aqueous-soluble prodrug with improved pharmacokinetic properties which may merit further development as a potential drug candidate." @default.
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• W2904754470 date "2019-11-01" @default.
• W2904754470 modified "2023-10-15" @default.
• W2904754470 title "Synthesis, characterization and in vivo evaluation of honokiol bisphosphate prodrugs protects against rats’ brain ischemia-reperfusion injury" @default.
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• W2904754470 doi "https://doi.org/10.1016/j.ajps.2018.11.004" @default.
• W2904754470 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7032162" @default.
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