| Objective The main purpose of this study was to illustrate the effect of traditional Chinese medicine borneol on the pharmacokinetics of antitumor drug CPT-11and the contents of monoamine neurotransmitter in brain. To investigate the borneol whether or not elevate the permeability of blood brain barrier and increase the brain drug concentration. Illuminated the influence mechanism of the borneol accelerated CPT-11through the BBB initially.Methods Rats were selected as experimental animal, CPT-11injection (control group), CPT-11with borneol (experimental group) was given by i.v. Blood and brain samples were taken at different time using mircodialysis sampling technique in jugular vein and hippocampus. The determination of blood and brain dialysates concentration of SN-38by LC-MS/MS method with Agilent Eclipse Plus C18(2.1mm×100mm,1.8μm) reversed phase column with acetonitrile-0.1%methanoic acid as mobile phase, and pharmacokinetic parameters were computed, preliminary analysis release characteristics via drug concentration-time curve. SD rats were randomly divided into five groups, blank (NS injection), given CPT-11injection (control group), CPT-11with different dosages borneol (experimental group). HPLC combined with electrochemical detector method was performed to detect HA and5-HT levels in microdialysates from rats’brain. Investigated the influence of different dosage borneol for CPT-11penetrating across BBB.Results To establish a method for determination of7-Ethyl-10-Hydroxycamptothecin (SN-38) in microdialysates from rats blood and brain. The blood pharmacokinetics results showed that control group:the t1/2is (2.25±0.54) h, Cmax is (431.14±22.85) μg/L, AUC(0-∞)is (1865.29±39.77) μg/L; experimental group:the t1/2is (3.39±0.62) h, Cmax is (498.62±29.17)μg/L, AUC(0-∞)is (1966.20±75.93)μg/L. The brain pharmacokinetics results showed that control group:Cmax is (78.06±7.96) ng/L, AUC(0-∞) is (760.91±44.87ng/L), Tmax is (2.25±0.14) h; experimental group:the t1/2is (5.77±0.94) h, Cmax is (122.±11.52) ng/L, AUC(0-∞)is (974.19±77.95) ng/L, Tmax is (1.75±0.22) h. HA and 5-HT results showd that the content of them were all stepped up to some extentdiffernt dosages.Middle dosage was more obvious than other dosages in HA results (P<0.05). It was no predominance between all dosages in5-HT results (P>0.05).Conclusion The technology of mircodialysis conbined with LC-MS/MS could carry out the monitoring in dialysates of the SN-38concentration in rats blood and brain. The technology of mircodialysis conbined with HPLC-ECD could carry out the monitoring of HA and5-HT contents. The investigation showed that, the borneol could increased the blood and brain drug level and elevated the AUC of SN-38; also, borneol stepped up the contents of HA and5-HT, but there was no difference between three dosages in5-HT results. It infered that borneol possible effect the neuroendocrine function to adjust physio-pathology action and then enhance drug reach through the blood brain barrier. It was possible one of the effect factors that the Borneol could accelerate transportation of CPT-11through the BBB with dose-effect relationship. |
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