Study The Effect Of Hepatic Microsomal Enzyme Induction

Aim: To study the effect of hepatic microsomal enzyme induction on the duration of action of
pentobarbital sodium.

Principle: The drugs induce hepatic microsomal oxidative enzyme systems to enhance the metabolism of other drugs. as a result, in the presence of an enzyme-inducer, the duration of action of the second drug will be reduced. This has significant clinical relevance because when more than one drug is administered at a time one drug may modify the action of another through the microsomal enzyme-inducing property.
The common drugs which induce hepatic microsomal enzyme systems are phenobarbitone and meprobamate. Co-administration of any drug with either of these drugs may affect the disposition of the second drug and therefore, the desired pharmacological effects. The students are advised to study various processes of drug metabolism before doing this experiment.

Requirement:
Animal: Mice(20-25g)
Drugs: Phenobarbitone sodium (dose: 50mg\kg IP, once a day for 5 days. Prepare a stock containing 5mg\ml of the drug and inject 1ml\100g of body weight of the animal. Prepare fresh solution every day). Pentobarbital sodium (dose45 mg\ml of the drug and inject 1 ml\100 g of body weight of the animal).

Procedure:

  1. Weigh and number the animals. divide them into two groups, each comprising of at least 6
    mice.
  2. To the first group inject phenobarbitone once daily for 5 days. To the second group inject
    distilled water, similarly, for 5 days.
  3. One hour after the last dose of phenobarbitone on the 5th day, inject pentobarbital to both the groups.
  4. Note the onset and duration of sleepdue to pentobarbital in both the groups as done in the
    earlier experiment.

The inference the animals pretreated with phenobarbital sleep for a shorter duration of the time as
compared to animals treated with distilled water.

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