Roche has announced that its AmpliChip CYP450 Test, which analyzes variations in two genes that play a major role in the metabolism of many widely prescribed drugs, has got the CE mark (Conformité Européene), allowing the test to be used for diagnostic purposes in the European Union.

The test detects genetic variations in the Cytochrome P450 2D6 and 2C19 genes and provides the associated predictive phenotype (poor, intermediate, extensive, or ultra-rapid metabolizer). Results can be used by physicians as an aid for selecting drugs and individualizing treatment doses for drugs primarily metabolized by the enzymes these genes encode. It is the first CE in vitro diagnostic test "Powered by Affymetrix" microarray technology, company says in a release.

"This specific test is the first representative of an exciting new technology which holds great potential for diagnostic applications," Heino von Prondzynski, Head of Roche Diagnostics and Member of the Roche Executive Committee said adding, "With the CE mark for the AmpliChip CYP450 Test, we are on our way to helping physicians move toward a more personalized approach to therapy, and to building our new line of chip-based diagnostics products."

According to the release, the AmpliChip CYP450 Test uses two industry standards, Roche polymerase chain reaction (PCR) amplification technology and Affymetrix high-density microarray technology (glass chips arrayed with tens of thousands of DNA fragments yet no bigger than a thumbnail). Affymetrix announced that its GeneChip System 3000Dx instrumentation, on which the AmpliChip CYP450 Test is run, is now also CE marked and available for diagnostic use in the European Union.

Enzymes encoded by the CYP2D6 gene metabolize many anti-depressants, anti-psychotics, anti-arrhythmics, pain drugs, anti-emetics, and beta-blockers (beta-adrenergic receptor blocker drugs). Enzymes encoded by the CYP2C19 gene metabolizes drugs from a variety of classes, including anti-convulsants, proton pump inhibitors, anti-coagulants, benzodiazepines, and anti-malarials.

Poor metabolizers treated with drugs that are extensively dependent on certain "normal" enzyme activity are at increased risk for excessive or prolonged levels of the drug in their blood (excessive or prolonged therapeutic effect) and toxicity, while ultra-rapid metabolizers may not achieve sufficient therapeutic levels in their blood with standard dosing. In the case of pro-drugs (these are drugs that require enzymatic action before they become the therapeutic compound in the body), the opposite phenomenon occurs. In addition, drugs taken at the same time (concurrent medications) and other environmental factors such as diet can inhibit or induce Cytochrome P450 enzyme activity, the release says.

To allow highly accurate prediction of patient phenotype, the AmpliChip CYP450 Test has the ability to detect not just the presence of CYP2D6 gene duplications, but also to discern which variation of the gene (allele) has been duplicated. This specificity is important in correctly predicting the ultra-rapid metabolizer phenotype and avoiding potential mis-classification of the patients tested, the release added.