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Interactions between drugs can also be measured at lowest doses
Date:4/11/2013

ractions in study participants. Mass spectrometers are so sensitive that they are able to identify the drug in a single drop of blood. The scientists conducted a study on interactions in 12 healthy test persons taking the fungicide ketoconazole and the sedative midazolam simultaneously. For the study, they administered midazolamdoses of 0.0000001 g, which was 30,000 times lower than the amount used for therapy. Comparisons with higher doses revealed that the drugs behaved identically at all concentrations. Therefore, even a minimal concentration in the body is sufficient to reliably predict the extent of the interaction during normal use.

Inhibition of the liver enzyme measurable in the nanogram range

With the help of ultrasensitive mass spectrometers, the speed with which a drug is degraded can be measured. They are used wherever small amounts need to be detected in liquids, e.g., contamination in drinking water, doping agents or environmental toxins. To this end, a small amount of blood or other body fluid is withdrawn after certain time intervals in order to determine the remaining concentration of the drug. The mass spectrometer sorts the molecules and determines their concentration. Based on their characteristic properties, the drugs can be reliably identified. "For the first time, we have proven that with this technique, we are able to find drugs in the blood even at extremely low doses, and that we can quantitatively determine them and identify their interactions," Prof. Haefeli said.

In the published study, the team investigated the interaction between the sedative midazolam, which is metabolized in the liver by the protein cytochrome P450 3A, and the fungicide ketoconazole, a well-known inhibitor of this cytochrome. The inhibition of the cytochrome and, in turn, the reduced degradation of midazolam, were already precisely measured in the nanogram dose. This interaction in particular plays an important role for patients wh
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Contact: Walter E. Haefeli
walter.emil.haefeli@med.uni-heidelberg.de
49-622-156-8740
Heidelberg University Hospital
Source:Eurekalert

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