Study on the pharmacokinetics, tissue distribution and excretion of laurolitsine from Litsea glutinosa in Sprague-Dawley rats

• Published in: Pharmaceutical biology 2021-01, Vol.59 (1), p.882-890
• Main Authors: Tan, Yin-Feng, Wang, Rui-Qi, Wang, Wen-Ting, Wu, Ying, Ma, Ning, Lu, Wei-Ying, Zhang, Yong, Zhang, Xiao-Po
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animal models; Animals; Aporphine alkaloid; Aporphines - isolation & purification; Aporphines - pharmacokinetics; Bioavailability; Biological Availability; Chromatography, Liquid - methods; Excretion; Feces; Gastrointestinal tract; Half-Life; Intravenous administration; Kidneys; LC-MS/MS; Litsea - chemistry; Male; Pharmacokinetics; Rats; Rats, Sprague-Dawley; Rodents; Tandem Mass Spectrometry - methods; Tissue Distribution; Urine
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2021.1944221

Laurolitsine is an aporphine alkaloid and exhibits potent antihyperglycemic and antihyperlipidemic effects in ob/ob mice. To investigate the pharmacokinetics, tissue distribution and excretion of laurolitsine. A LC-MS/MS method was established and validated to determine laurolitsine concentrations in the biological matrix of rats (plasma, tissue homogenate, urine and faeces). 10 Sprague-Dawley (SD) rats were used for plasma exposure study: 5 rats were injected with 2.0 mg/kg of laurolitsine via the tail vein, and the other 5 rats were administered laurolitsine (10.0 mg/kg) by gavage. 25 SD rats used for tissue distribution study and 5 SD rats for urine and faeces excretion study: rats administered laurolitsine (10.0 mg/kg) by gavage. After administered, serial blood, tissue, urine and faeces were collected. Analytical quantification was performed by a previous LC-MS/MS method. The pharmacokinetics, bioavailability, tissue distribution and excretion of laurolitsine were described. The pharmacokinetic parameters of oral and intravenous administration with T max were 0.47 and 0.083 h, t 1/2 were 3.73 and 1.67 h, respectively. Oral bioavailability was as low as 18.17%. Laurolitsine was found at a high concentration in the gastrointestinal tract, liver, lungs and kidneys (26 015.33, 905.12, 442.32 and 214.99 ng/g at 0.5 h, respectively) and low excretion to parent laurolitsine in urine and faeces (0.03 and 1.20% in 36 h, respectively). This study established a simple, rapid and accurate LC-MS/MS method to determine laurolitsine in different rat samples and successful application in a pharmacokinetic study.