Dissertation > Excellent graduate degree dissertation topics show

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
Read: Download Dissertation

Abstract


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

Related Dissertations

  1. Research on Fault Detection and Network Reconfiguration Algorithms for Distribution Network,TM727
  2. Modeling of Sea Clutter and Effect of Sea Clutter on Isar Imaging,TN957.54
  3. Simulation and Experimental Study on the Scattering Properties of Two Dimensional Rough Surfaces,TP391.41
  4. Modeling Internet Link Delay Based on Measurement,TP393.4
  5. The Research on Space Layout of Characteristic Economy in Wenshan,F127
  6. Effects of the Exotic Invasive Plant Solidago Canadensis L. on the Community Structure of Soil Anmals,S451
  7. Chinese Sports Athletes Human Capital Development and Income Distribution Research,G812.0
  8. Based on statistics of the lognormal distribution heteroscedasticity model inferred,O212.1
  9. Research on Intellectualized Diagnostic Device Applied to Distribution Lines,TM755
  10. Soil Organic Carbon Fractions and Its Dynamic in Different Soil Types of Wuyi Mountains,S153.6
  11. Research on Rainfall Erosivity in Jiangsu Province,S157.1
  12. Studies on Leaf Epidermal and Pollen Micro-morphology and Geographical Distribution of the Genus Euonymus of Henan,Q944
  13. Study on the Distribution Pattern and Priority Areas of Endangered Terrestrial Animals in Jiangsu Province,Q948.2
  14. Sagitta Morephology, Distribution, Biology and Stock Assessment of Four Prlagic Species in the Mouth of Beibu Gulf,S932.4
  15. Community impact study of the distribution of benefits mechanism of development of ethnic village,D422.6
  16. Based on the Layout and Adjustment of Rural Primary and Secondary School Students to Go to School, the Traffic Problem Investigation and Strategy Research,G639.2
  17. The Influence of Long-term Regular Exercise to the Distribution and Change Regulation on Human Skin Temperature,G804.2
  18. A Smoothing Method for Solving Model under WCVarR,O224
  19. Cadmium, Chromium and Lead Accumlation, Distribution in Aralia Elata Var. Inermia and Their Effect on Leaf Antioxidative System,S792
  20. Research and Simulation on Droplet Distribution in φ38mm Pulsed Sieve-Plate Extraction Column,TQ028.3
  21. The Studying of Temperature Distribution and Control Technique during Polymer Sheet Heat Process,TQ320.6

CLC: > Medicine, health > Pharmacy > Pharmacology
© 2012 www.DissertationTopic.Net  Mobile