Pharmacokinetics, tissue distribution, and safety evaluation of a ligustilide derivative (LIGc)

Publication date: Available online 31 January 2020Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Yanxia Zhang, Yaming Zhang, Yanming Han, Ye Tian, Pengcheng Wu, Aiyi Xin, Xiaoning Wei, Yanbin Shi, Zhenchang Zhang, Gang Su, Yanping Shi, Junxi LiuAbstractLigustilide (LIG) is the main active ingredient of Angelica sinensis (Oliv.) Diels and has a neuroprotective effect against ischemic stroke. However, owing to its multi-conjugated unstable structure, the compound has poor drug-forming properties. Therefore, we synthesized highly stable colorless needle crystals (known as ligusticum cycloprolactam, LIGc) through the structural modification of LIG. After a stability experiment was conducted at room temperature for four months, no impurity peaks were found by HPLC-DAD analysis, which indicated that LIGc resolved the stability issues of LIG. LIGc was absorbed and eliminated rapidly after intravenous administration (Cmax = 6.42 ± 1.65 mg/L at a dose of 20 mg/kg) and oral administration (Tmax = 0.5 h, Cmax = 9.89 ± 1.62 mg/L at a dose of 90 mg/kg, t1/2z approximately 2.5 h). The absolute oral bioavailability (F) of LIGc was clearly higher than the F of LIG reported in the literature (F, 83.97% versus 2.6%). Linear dose-dependent pharmacokinetics were observed after oral administration, with a higher area under the curve (AUC0-t, 22.31 ± 2.88 mg/L*h) observed at 90 mg/kg than that at 45 mg/kg (AUC0-t, 13.673 ± 0.66...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research