Synthesis, characterization and in vivo evaluation of honokiol bisphosphate prodrugs protects against rats' brain ischemia-reperfusion injury.

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

SUBMITTER: Xu G 

PROVIDER: S-EPMC7032162 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature