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Studies on the Effects of Borneol on the Pharmacokinetics and Biopharmaceutics of Rifampicin

Author: WuShouRong
Tutor: ChengGang;CuiFuDe
School: Shenyang Pharmaceutical University
Course: Pharmacy
Keywords: borneol rifampicin pharmacokinetic blood-brain barrier combination drug therapy small intestinal absorption kinetics distribution.
CLC: R96
Type: Master's thesis
Year: 2002
Downloads: 315
Quote: 0
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Based on the Traditional Chinese Medicine documents, borneol given orally could significantly promote the absorption of other drugs for central nervous system disease, and enhance the concentration of some drugs in brain. In the therapy of central nervous system disease, borneol was well studied.A new HPLC method was developed to measure the rifampicin concentration in rat plasma and the brain, plasma, lung, live, kidney in mice. The detection limit, the precision for within-day and between-day, the extraction recoveries of this method were good enough to be used in the pharmacokinetics and biopharmaceutics study of rifampicin. We used this RP-HPLC method to determine the concentration of rifampicin in all biosamples.In this paper, the effects of borneol on the pharmacokinetics and biopharmaceutics of rifampicin were studied. Firstly, the improved intestinal absorption experiments of rat were used to study the effects of borneol on the intestinal absorption kinetics of rifampicin. The absorption kinetics and permeability rate constants (ka) were investigated by the in situ perfusion method in rats. The result demonstrated that ka were 0.129 8 0.026 4 h-1 and 0.0934 0.012 9 h-1, and the uptake rate were 11.211 5 2.356 2%, 7.598 5 1.441 1%, respectively. The intestinal absorption of rifampicin was possibly involved in the passive diffusion and first order kinetics. It wasABSTRACTfound that the intestinal uptake rat ( PA ) of rif ampicin was increased with the increase of the concentration of borneol, but the peameability rate constant (Ka) was not influenced by the concentration of borneol. It indicated that borneol could significantly enhance the absorption of the rifampicin in rat intestines. Secondly, the effects of borneol on the pharmacokinetics of rifampicin were evaluated by in vivo pharmacokinetics in rat. By a cross-over design, six rats were given i.g. rifampicin 20 mg-kg-1 with or without previous borneol 20 mg-kg-1 after overnight fast. The rifampicin in rat’s plasma was determined by the RP-HPLC method and the pharmacokinetics parameters were calculated by 3P97 software. The results demonstrated that t1/2ka were 18.36 min and 22.70 min, respectively, and t1/2ke were 569.79 min and 435.52 min, respectively. The peak plasma levels were 12.62 g-mL-1 at 94.03 min and 8.70 g-mL-1 at 102.06 min, respectively. The area under the plasma concentration time curves was 11 630.64 g-min-mL-1 and 6 432.80 g-min-mL-1, respectively. The results showed that the borneol could significantly enhance the in vivo absorption of the rifampicin.The distribution experiment in mice was undertaken to evaluate whether borneol could enhance the permeation of rifampicin to brain. After i.g. administration of rifampicin in mice, the drug concentrations in the different tissues were determined by RP-HPLC. The results showed that the AUC of rifampicin in the group administrated only rifampicin was the highest in liver, followed by kidney, plasma, lung, brain; the MRT of rifampicin was the highest in kidney, followed by liver, lung, brain, plasma. In the other hand, the AUC of rifampicin in the group previously combined with borneol was the highest in liver, followed by kidney, plasma, lung, brain; the MRT ofABSTRACTrifampicin was the highest in liver, followed by kidney, lung, plasma, brain. The sequence of peak concentration in plasma is the same for both groups, followed by liver, kidney, plasma, lung, brain. It demonstrated that borneol given orally could significantly promote the absorption of rifampicin in rat and mice, especially, enhance the concentration of rifampicin in the mice’ brain.At the same time some physicochemical properties of rifampicin were studied. The solubility increased in DMSO, methanol, acetonitrile, methylenechloride, but it cannot be solved in water. The Po/w of rifampicin changedwith the different pH. There is the peak value of Po/w between pH 4.5 andpH 6.81. The pKa1 of the drug was about 1.86. The mean plasma protein binding ratio of rifampicin

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