Comparison of pharmacokinetics and tissue distribution of diosbulbin B in rats after intragastric administration of compound diosbuIbin B and ethanol extract from Dioscorea bulbifera L / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To characterize pharmacokinetics and tissue distribution of diosbulbin B (DIOB)in rats,and compare exposure and elimination of DIOB in plasma and tissues after ig adminis-tration of compound DIOB and ethanol extract of Dioscorea bulbifera L.(EEDB),respectively.METHODS Liquid chromatography coupled with tandem mass spectrometry method was developed and validated for quantitative determination of DIOB in plasma and tissue samples. The sensitivity, matrix effect, accuracy and precision of the method were determined. After a single ig administration of DIOB 1.3 mg·kg-1and EEDB 1.0 g·kg-1, respectively, plasma and tissues samples were collected separately from male SD rats at prescheduled time points.The drug-protein binding of DIOB in plasma and tissues was measured using Rapid Equilibrium Dialysis Assay. The concentration-time profiles of DIOB were analyzed using WinNonLin 6.4 to obtain pharmacokinetic parameters. RESULTS Rapid absorption and elimination of DIOB were observed in rats.The plasma maximum concentration(cmax),peak time(tmax) and eliminate half life(t1/2)of DIOB in rats receiving DIOB or EEDB were 312±67 and(131±84)μg·L-1(P<0.01), 0.12 ± 0.07 and (0.23 ± 0.17) h, and 1.17 ± 0.28 and (2.34 ± 0.83) h (P<0.05). DIOB was rapidly distributed in most tissues,with the AUC(0-24 h)of DIOB in lungs,liver and kidneys for DIOB and EEDB groups were 4527.0±557.7,183.0±51.1 and(64.4±22.4)ng·h·g-1,and 6507.9±424.3(P<0.01),467.5±202.7(P<0.05) and (238.6 ± 70.0) ng·h·g-1(P<0.05), respectively. The protein binding rate of DIOB was 38.7%-43.6%,61.3%-66.9% and 61.4%-64.7% in plasma,livers and lungs,respectively.The ratio of free concen-trations between tissue and plasma for lungs was more than 48,indicating the specific distribution of DIOB in lungs.CONCLUSION There is difference in pharmacokinetics and tissue distribution of DIOB in rats after taking compound DIOB and EEDB.Among the tissues detected,lungs are the major target of DIOB with the highest exposure level.These characterizations should be considered in pharmacological and toxicological studies of DIOB and relevant herbs.