| Objectives: 1) To establish an RP-HPLC method for the quantitative determination of clindamycin in rabbit plasma and tissues. 2) To determine the effects of Achymthes bidentata Blume on the pharmacokinetics parameters of Clindamycin in New-Zealand rabbits. Method: After Samples were deproteinized with acetonitrile and degreased with n-hexane, clindamycin was extracted with dichloromethane from samples. analytical column : C18 reversed-phase column ; mobile phase: acetonitrile(contained 12.5mmol tetra-n-butylamMolonium hydrogen sulfate)- phosphate buffer(contained 10 mmol Na2HPO4 and 20mmolKH2PO4, pH=3.50) (20/80,v/v) ; column temperature: 40℃; flow rate: lmL/min. For study of concentrations of clindamycin in plasma, 20 rabbits were divided randomly to experimental group and control group, 10 both groups. For study of drug concentrations in tissues, 44 rabbits were divided randomly into an experimental group and a control group, 22 both group. Both control groups were administrated 20mg/kg.b.w clindamycin, and both experimental groups were administrated 20mg/kg.b.w. clindamycin and 2g/kg.b.w. Achymthes bidentata Blume decoction simultaneously. Blood samples were got at 0, 0.167,0.333,0.5,0.75,1,2,4,6,8 and 12h after administration. Tissue samples were got at 0, 0.25,0.5,0.75,1,2,3,4,6,8 and 12h after administration, two rabbits being executed to take cardia, hepar, lung and kidney at every time point in each group.Concentrations of clindamycin were determined by reversed phase high-performance liquid chromatography in samples. Pharmacokinetics parameters were evaluated by 3P97 pharmacokinetics programme. Parameters were analyzed by SPSS (12.0)software. Results: The assay was validated from 80 to 40000ng/mL. Good linearity was observed in the entire concentration range. The limit of quantification (LOQ) was 80ng/mL. Regression of accuracy data yielded an overall mean recovery value of 91.0— 93.6%, and precision data revealed coefficient of variation (CV %) values was lower than 5.45%. For the control group , the drug concentration-time data were fitted to atwo-compartment model with first order absorption after a single oral administration of clindamycin; Tp was 0.497±0.099h, Cmax was 4.257 + 0.793 mg/L, AUC was 46.262± 15.427mg/L ?h, Vd was 3.215±0.682L/kg, CL(S) was 0.339±0.103mg/L, Ti/2pwas 8.701 ±2.756h. For the experimental group, the drug concentration-time data were also fitted to a two-compartment model with first order absorption after a single oral administration of clindamycin; Tp was 0.544 + 0.082h,Cmax was 1.307 + 0.237mg/L, A UC was 19.18±6.44mg/L *h, Vdwas 10.59±1.51L/kg, CL(J)was 0.544±0.178mg/L, Tm? was 16.19 ±4.27ho Conclusions: The RP-HPLC method described in the text were applicable to determine clindamycin in plasma and tissues of rabbit cardia, hepar, lung and kidney. Clindamycin was widely distributed after administrated to rabbit by oral. Achymthes bidentata Blume decoction can increase concentrations of clindamycin in cardia, hepar, lung and kidney; can influence pharmacokinetics parameters of clindamycin in rabbits. |
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