Drug metabolism

Making use of pharmacogenetic knowledge depends upon; a) understanding the relative significance of genetic vs. other sources of variation (environmental, physiological and pathological) and b) the ability to correlate genotype with clinical response.

Pharmacogenetic tests have been used retrospectively to explain unusual responses and in prospective studies involving small panels of pre-genotyped subjects. We are observing currently an increase in demand for preselecting patients for clinical trials on the basis of phase I or phase II enzyme polymorphisms, particularly in the case of phase I clinical trials.

Geneblitz® offers its clients a number of test assays, including the following:

Drug Metabolism genes

We offer a comprehensive range of in-house tests to help companies better understand the metabolism, efficacy and safety of new therapeutics. A list of assays currently offered are found here

Drug-specific target genes

Assays to detect a known gene variant/SNP/allele that will predict an individual’s response to a specific drug e.g. ApoE genotyping.

Custom assays

If you cannot find your gene of interest on our list, then please contact us as we also offer an assay design, development and validation service in line with current regulatory requirements. We can take your project from initial design and feasibility testing, including advice on SNPs of choice through to its end-use in samples from clinical trials.

The Value of Genotyping in Clinical Development

Measuring the genetic variation within a clinical trial population can improve the design and increase the value of the trial by:

Pre-selecting patients most likely to benefit from the proposed therapy
Reducing the size of the clinical trial by using a defined population with an improved chance of a good response
Understanding the results of the trial in terms of the individual differences of the trial population

The consequences of not understanding metabolic variability in clinical trials can be considerable:

Drugs may fail late in clinical development
Iatrogenic disease may occur, i.e. there may be drug associated morbidity and mortality
There may be restrictions placed on drug use
A drug may be withdrawn from the market

Variation in pharmacokinetics, predominantly due to genetic polymorphisms in the drug metabolising enzymes is responsible for part of this metabolic variation. That the metabolism of a drug is determined by enzymes which exhibit polymorphism is not a priori a reason to curtail its development despite there perhaps being substantial pharmacokinetic variability.

As with many biological systems there is redundancy in the drug metabolism enzyme system. The successes to date have to some extent been based on large effects such as those revealed by CYP2D6 genotype profiles. Most drugs however, are cleared by multiple pathways, i.e. are not metabolised solely by a single enzyme. We consider that the study of polygenic polymorphisms in the drug metabolising enzymes will become of increasing importance.

Please click here for further information on the phase I and phase II enzymes.

We also offer services such as Residual DNA, Genotyping, Forensic Testing, Gene Expression and various other services. Please click here to contact us with your requirements.

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