ABSTRACT
Objective To investigate the toxicokinetic properties of ginkgolide B(GB) injection after single or repeat-ed administration by intravenous drip in Beagle dogs and to provide evidence for its rational use. Methods Beagle dogs were randomly divided into three groups,and received GB injection at big,medium and small doses of 80,20 and 5 mg·kg-1, re-spectively,by iv drip for 30 min per day and for 6 consecutive days per week for up to 91 days.The blood samples of Beagle dogs were drawn at different time points on the first and last day of administration,and concentrations in plasma were detected by GC-MS method.Toxicokinetic parameters were calculated by DAS pharmacokinetic software and statistically analyzed by SPSS 11.5 software. Results The elimination half-life (t1/2β) of GB at single dose of 5,20,80 mg·kg-1were(110.2±32.6),(115.4± 12.8),(98.6±26.8) min, respectively.The AUC0-twere (61.1±7.4), (348.6±90.5), (2 046.2±356.4) mg·L-1·min,re-spectively.The t1/2βof GB at mutiple doses of 5,20,80 mg·kg-1on the 91rd day were (117.9±28.0),(118.2±17.0),(120.5± 49.4) min,respectively.The AUC0-twere (67.9±14.9), (218.3±31.8), (1 986.4±426.6) mg·L-1·min, respectively.There was no significant difference in main toxicokinetic parameters including t1/2βamong the single or repeated dosage groups, but AUC0-tand Cmaxincreased proportionally with doses. Conclusion The curves of single and repeated intravenous drip of GB in-jection in beagle dogs were in line with the two atrioventricular model,with linear dynamic characteristics and there was no accu-mulation of repeated drug delivery in the body.