Abstract

Rhynchophylline (RHY) is a pharmacologically active substance isolated from Uncaria rhynchophylla which has been used to treat cardiovascular and central nervous system diseases. Microdialysis (MD) technique is a continuous, real-time sampling technique that is very suitable for the evaluation of drug disposition.  The present study coupled an in vivoMD sampling method with reliable high performance liquid chromatography (HPLC) to determine free RHY in blood. MD probes were inserted into the jugular vein of rats, and blood dialysates were collected at 15-min time intervals for 8 h after intravenous administration of RHY (15 or 25 mg/kg). The method has been validated with good linearity, specificity, accuracy (RE 2.6 to 5.6%) and precision (98.96 to 100.57%) of MD probe recovery. RHY was chemically stable during storage and assay procedures. The pharmacokinetic parameters of unbound RHY were described as: The area under curve (119.96 ±19.29 min/μg/ml, 222.13 ± 27.60 min/μg/ml), T1/2 (46.17 ± 9.18 min, 47.97 ± 9.33 min), mean residence time (65.45 ± 9.15, 69.48 ± 9.45 min) and C_max (1.55 ± 0.36, 2.62 ± 0.29 μg/ml). All PK parameters showed positive dose-dependent correlation. In addition, RHY showed a high degree of drug–protein binding. MD sampling may be valuable for pharmacokinetic studies of medicinal plants.

Key words: Microdialysis sampling, rhynchophylline, pharmacokinetics, liquid chromatography, drug–protein binding rate.