Font Size: a A A

Studies On The Transports And Pharmacokinetics Of Andrographolide In Rats

Posted on:2010-10-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z Y DingFull Text:PDF
GTID:1114360272996745Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
The medicinal plant Andrographis paniculata (Burm.f.) Nees plant is found in many Asian countries. Andrographolide(Andr) is one of the principal constituents of Andrographis paniculata (Burm.f.) Nees, used for the treatment of fever, cold, inflammation, diarrhea and other infectious diseases. Andrographolide also has many other bioactivities, such as antimicrobial activity , anti-platelet aggregation, inhibits growth of acute promyelocytic leukaemia cells by inducing retinoic acid receptor-independent cell differentiation and apoptosis , anti- HIV, choleretic action, anti-fertility Property , induces cell cycle arrest at G2/M phase and cell death in HepG2 cells via alteration and scavenge free radicals by donating the allylic hydrogen of the unsaturated lactone ring. In generally, Andrographolide take orally .However, Andrographolide have low aqueous solubility, bitterness and first pass effect lead to poor bioavailability when used for clinical treatment. As far as the factors affecting drug absorption, distribution, metabolism and excretion (ADME) are concerned, plasma membrane transport is one of the most important. The molecular mechanism of drug transport is very important as far as the bioavailability and targeting efficiency are concerned. This is the chemical structure of Andrographolide.Fig. 1. Chemical structure of AndrographolideIn the present study, we formulated Biopharmaceutics and Pharmacokinetics of Andrographolide. The main objective of the study was to research ADME of Andrographolide.Transdermal drug delivery was one of the principal constituents of disquisition.This study was conducted to determine parameters of physical and chemistry, the membrane transport of Andrographolide in rats to take orally and to evaluate infection of stomach content for absorption, distribution, Plasma Protein Binding , metabolism, and excretion of Andrographolide. Inclution compound ofβ-cyclodextrin and solid dispersion(SD)were preparated and dissolutions were determined. We found that dissolution of Inclution compound ofβ- cyclodextrin of Andrographolide was the fastest in its . In the present study absorption , distribution, metabolism, and excretion of Andrographolide in rabbits following muscle injection and trandermal drug delivery were evaluated. Time-course each tissue and blood and excreta were collected and determined. The drug concentration levels were determined by HPLC for Andrographolide. Andrographolide is first order precesses absorption in the small intestine. The absorption rate constant of Andrographolide was 0.0067h-1. Stomach content effected-absorption of Andrographolide in rats. Following transdermal drug delivery and muscle injection application, Transdermal drug delivery plasma levels of Andrographolide was high after the first 55 min. After muscle injection the drug concentration levels were lower than transdermal drug delivery. On the other hand, the absorbed Andrographolide did not accumulate in tissues; only a few of the administered dose was found in liver, spleen and kidney. Most of the applied Andrographolide was excreted in urine. This fact strongly suggests that transdermal drug delivery is better way than to take orally for Andrographolide. More studies in mammalian species are necessary in order to understand the pharmacokinetic behavior of Andrographolide. Plasma protein binding rate of Andrographolide was 5.86% .It is not strength .Electroporation to enable successful transdermal drug delivery for Andrographolide . We concluded that this study provided a scientific basis for the use of andrographolides in clinical therapy and offered important parameters that could be used in the design of a new class of preparations.
Keywords/Search Tags:Andrographolide, ahsorption, distribution, excretion, Pharmacokinetics
PDF Full Text Request
Related items