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In vivo & vitro methods to predict drug absorption
Transcript of In vivo & vitro methods to predict drug absorption
Used to determine the permeability of drug using live animal tissues.
Assesses the major factor involve in absorption process& predict the rate &extent of drug absorption.
The intestine of lower experimental animals such as rats, guinea pigs, rabbits are taken for the study. Everted sac modification Circulation techniques Everted intestinal ring or slice techniques Advantages The epithelial cell of the mucosal surface are exposed directly to the oxygenated mucosal surface.
Prolongs the viability and integrity of the preparation after removal from the animal.
Convenience & accurate. Difficulty in obtaining more than one sample per intestinal segment. Disadvantage A number of different solutions may be tested with a single segment of the intestine.
Simple & reproducible.
Distinguishes between active & passive absorption.
It determines the region of the small intestine where absorption is optimal, in the case of active transport.
Used to study of pH , surface active agents, complexation & enzymatic hydrolysis. Advantages Disadvantages The intestinal preparation is removed from the animal as well as from its normal blood supply. Under this condition , the permeability characteristics of the membrane are altered.
The rate transport of drug as determined from the everted sac technique, is slower. Method is applicable to kinetic studies of the factors affecting drug absorption.
Both surface are oxygenated.
Eversion is not necessary. Advantages Simple & reproducible.
Kinetic studies can be performed. Advantages Disadvantages Lack of maintenance of viability in the isolated rings due to absence of blood supply and nerves. Gives us an idea about some important factors that influence absorption such as gastric emptying, intestinal motility & the effects of drugs on the GIT can be determined. Everted small intestinal sac technique Direct method Indirect method The drug level in blood or urine is determined.
For this, sensitive reproducible analytical procedure should be develop to determine the drug in the biological fluid that is sampled. Blank urine or blood sample is taken from the test animal. The test dosage form is administered to the animal & at the appropriate interval of time the blood or urine samples are collected & assayed for drug content. From the data, we determine the rate & extent of the drug absorption. When the measurement of drug concentration in blood or urine is difficult or not possible pharmacological response of the drug is related to amount
of a drug in the body determine. The response is determine after the administration
of a test dosage form.