Methods for the Study of Drug Biotransformation

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Chapter: Biopharmaceutics and Pharmacokinetics : Biotransformation of Drugs

Methods for the Study of Drug Biotransformation : In Vitro Methods, In Vivo Methods


In Vitro Methods

There are several approaches to in vitro drug metabolism studies. The enzyme sources in these studies are human-derived systems currently under rapid development and evaluation. These systems consist of –

·           Liver microsomes

·           Hepatocytes and cell lines heterologously expressing drug-metabolising enzymes

·           Liver slices, and

·           Individually cDNA-expressed enzymes in host cell microsomes.

In these studies, the extent of uptake of drug is determined from the steady-state concentration in tissue and free concentration in the perfusate. The composition of the perfusate and the rate of perfusion are important experimental determinants of the rate of uptake of drug by the liver.

In Vivo Methods

Investigations of biotransformation pathways in vivo require the collection and analysis of appropriate biologic samples. The types of sample collected include urine, faeces, expired air, blood/plasma, bile, milk, saliva, synovial fluid and tissues. These samples can be divided into two groups –

1. Those requiring complete collection e.g. urine and faeces.

2. Those which are sampled at regular intervals of time e.g. blood.

The two approaches to identification of metabolites in the collected samples are –

1. Identification of metabolites in the biologic samples when reference compounds are available.

2. Isolation and identification of all major metabolites regardless of the availability of reference compounds. This approach requires a method of detecting metabolites such as use of radiolabelled form of the drug. Radiolabelling is done at a metabolically stable position. HPLC and TLC techniques are employed to detect and measure the radiolabelled metabolites.

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