Pharmacokinetics, biodistribution and bioavailability of isoliquiritigenin after intravenous and oral administration

Abstract

Context: Isoliquiritigenin (ISL) has been shown to exhibit a variety of biological activities. However, there is little research on the pharmacokinetic behavior and tissues distribution of ISL. Objective: Pharmacokinetics, biodistribution and bioavailability of ISL after intravenous and oral administration were determined by systematic investigation in Sprague-Dawley rats. Materials and methods: ISL was dissolved in medicinal ethanol-Tween 80-0.9% sodium chloride saline in a volume ratio of 10:15:75. The ISL solution was injected in rats via a tail vein at a single dose of 10, 20 and 50 mg/kg and administered orally in rats at a single dose of 20, 50 and 100 mg/kg, respectively. Blood samples were collected at time intervals of 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8 and 12 h after intravenous injection. Tissues of interests in mice were collected immediately at each determined time point (0.5, 1, 2, 3 and 6 h) after cervical dislocation. Results: The dose-normalized AUC values were 7.3, 7.6 and 8.7 mg  h/ml (calculated based on the dose of 10 mg/kg) for intravenous doses of 10, 20 and 50 mg/kg, respectively. The elimination half-lifes (t 1/2 ) were 4.9, 4.6 and 4.8 h at 10, 20 and 50 mg/kg intravenous doses, respectively. The F values were 29.86, 22.70, 33.62% for oral doses of 20, 50 and 100 mg/kg, respectively. Liver, heart and kidney were major distribution tissues of ISL in mice. The plasma protein binding of ISL in rats was 43.72%. Conclusion: The work may useful for further study of the bioactive mechanism of ISL.

Isoliquiritigenin induces apoptosis and autophagy and inhibits endometrial cancer growth in mice

“…Therefore, intravenous administration of ISL was more effective than oral administration [11]. Regardless of the delivery method of ISL, the absorption rate and discharge rate are rapid [43]. …”

The application of HPLC‐MS/MS to studies of pharmacokinetics and interconversion of isoliquiritigenin and neoisoliquiritigenin in rats

“…The lower limit of quantification (LLOQ) was defined as the lowest drug concentration (1 ng/mL), which was much lower than the 19 ng/mL reported previously (Qiao et al , ). At this LLOQ, the signal‐to‐noise ratio was >10, and the accuracy and precision were 93.83 and 6.29% for ISL, and 92.17 and 5.23% for NIS, respectively.…”

“…Compared with the numerous studies on pharmacological activities, only a few reports have explored the pharmacokinetic characteristics of ISL. Several methods have been reported for the biomedical analysis of ISL, including synchronous fluorescence spectrometry (Han et al , ), capillary electrophoresis (Cao et al , ) and HPLC (Qiao et al , ). However, sample separation for determination of ISL is tedious and expensive for synchronous fluorescence spectrometry and capillary electrophoresis.…”

“…However, sample separation for determination of ISL is tedious and expensive for synchronous fluorescence spectrometry and capillary electrophoresis. The pharmacokinetics of ISL have been investigated with HPLC following intragastric administration (Qiao et al , ), but ISL was dissolved in medicinal ethanol‐Tween 80–0.9% sodium chloride saline in a volume ratio of 10:15:75, which might alter the absorption of ISL. Furthermore, the LLOQ of the HPLC method was 19 ng/mL.…”

Pharmacokinetic Profiles of Active Components After Oral Administration of a Kampo Medicine, Shakuyakukanzoto, to Healthy Adult Japanese Volunteers

“…The second low‐concentration peaks of these components were observed 2–3 h after the oral administration of SKT. Because this bimodality was not observed during animal tests in the case of intravenous administration, the cause is not considered to be enterohepatic circulation. This bimodality of ILG is surmised to be because of a difference in the absorption site of ILG and isoliquiritin metabolite because ILG is also produced from the glycoside isoliquiritin by enteric bacteria .…”