Molecular Diagnostics Services, Inc.
A Contract Research Organization

Metabolism Assays:

In vitro Assays for Human Drug Metabolism

Using human tissue in vitro metabolism and absorption studies as key features of the drug discovery and development process. Our project managers are available to assist with development of study designs and data interpretation. We conduct your studies in a GLP environment, while applying our experience and knowledge to your particular ADME problem to move your drug or vaccine efficiently through the development process.

In Vitro Absorption and Metabolism Models

In vitro models to predict drug absorption and metabolism are valuable techniques for both screening new drug candidates, and later evaluations of potential drug-drug interactions. MDS offers the following services

Comparative Metabolism and In Vitro Toxicity Studies

Drug-Drug Interaction Studies

Determination of Cytochrome P450 Form-Specific Metabolism Measure metabolism of form-specific substrate Correlation assay with six form-specific activities Confirmation with microsomes from cells expressing single form of human P450

Cytochrome P450 Inhibition Three drug concentrations Pooled human liver microsomes from six donors Six P450 form-specific assays for CYP1A, 2A6, 2C9, 2C19, 2D6, and 2E1

Cytochrome P450 Induction:
Peroxisome Proliferation Studies: Palmitoyl CoA-Oxidation:

Rat Hepatocytes

Human Hepatocytes
Cytotoxicity Assays In Primary Cultures:

Screening Assays
Enzyme Release (lactate dehydrogenase)

MTT Conversion (Mitochondrial Function)

Available Species: Human Rat Dog Rabbit Mouse Guinea pig Hamster Nonhuman primates

Specific functional assays: Available for determining chemical mechanism of action and include urea synthesis, protein synthesis, lipid peroxidation, and oxygen consumption, among others.

Hemolytic Potential and Compatibility Assays:

Hemolytic Potential in Rat or Dog Blood Whole rat or dog blood is exposed to the test article and the amount of hemoglobin released from lysed cells is determined spectrophotometrically Untreated controls, vehicle controls, and positive controls are included Known volumes of whole blood are used to generate a standard curve representing 0% to 100% hemolysis

Hemolytic Potential in Human Blood Same as M108 but using human blood

Hemolytic Potential in Rat, Dog, and Human Blood Same as M108 but using blood from all three species

Optional Plasma and Serum Compatibility:

Compatibility is determined by adding the test article to plasma and serum, individually, and then assessing the occurrence or non-occurrence of precipitation or coagulation of plasma or serum protein

Comparative Metabolism and In Vitro Toxicity Studies

Incubation with In Vitro Preparations: Liver, kidney, small intestine from humans, dogs, monkeys, or rodents. Isolated cells, tissue slices, or subcellular fractions (S9, microsomes, or cytosol, with cofactors)
In Vitro Assays
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©2007 Molecular Diagnostic Services, Inc.