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

Clinical pharmacologists at Heidelberg University Hospital have achieved major progress for improving the reliability of drugs. In a pharmacological study, they showed for the first time that interactions between drugs can be detected with minute doses in the range of nanograms. However, at these low doses, the drugs are neither effective nor do they have side effects. This means that studies on interactions occurring in drug combinations can be conducted practically without posing risks or negative impacts on the participants. This is true not only for healthy volunteers, as has been observed to date, but also for patients. The study was published in the medical journal Clinical Pharmacology & Therapeutics.

"Many chronically ill or elderly patients today take several different drugs. Around two percent of all hospital stays in Germany are the result of interactions between the drugs," said Professor Walter E. Haefeli, Medical Director of the Department for Clinical Pharmacology and Pharmacoepidemiology at Heidelberg University, where the new technique of "nano-dosing" has been developed and tested. "Many interactions could be avoided if we were aware of them and took them into account."

Drug combinations rarely studied for interactions

However, very few drug combinations have been systematically tested for interactions to date. "Many risks remain unknown to date and need to be studied," Prof. Haefeli explained. After initial tests conducted in animals, combinations are currentlybeing studied in healthy participants with the usual therapeutic doses. Depending on the drug, this can strongly impact the body. Furthermore, a healthy person may react differently to a drug than a sick person does. This means that study findings can only be transferred to a limited extent.

Using mass spectrometry, an ultrasensitive technique, the team led by Prof. Haefeli succeeded in drastically reducing the dose for studies on interactions 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 who need to take several drugs simultaneously. Many drugs inhibit this enzyme, which metabolises around half of all regularly used medicines. However, if a drug is degraded too slowly, at normal doses, it accumulates in the body and, in the worst case, can cause toxicity.

Further studies planned

Prof. Haefeli and his team are now testing the new method in patients. "Since we can use minimal drug doses, these studies are also safe for patients," Prof. Haefeli explained. Heidelberg University pharmacologists will also examine the interactions of other medications that influence other metabolic enzymes. "The method could also be used in the many studies in which interactions are relevant for approval by the authorities, for instance," said Prof. Haefeli, looking toward the future.


'/>"/>

Contact: Walter E. Haefeli
walter.emil.haefeli@med.uni-heidelberg.de
49-622-156-8740
Heidelberg University Hospital
Source:Eurekalert

Related medicine news :

1. Novel technique demonstrates interactions between malaria parasite and HIV
2. Stanford/Intel study details power of new chip to diagnose disease, analyze protein interactions
3. Survey shows medical students have frequent interactions with pharmaceutical companies
4. Study finds significant skull differences between closely linked groups
5. Study: No link between depression, nasal obstruction
6. AADR comments on review that validates association between oral health and heart health
7. New research finds no association between white potato consumption (baked, boiled mashed) and obesity, Type 2 diabetes or systemic inflammation
8. Study shows link between pre-pregnancy obesity and lower test scores
9. First study investigating possible link between sunscreen ingredient and endometriosis
10. Early Study Hints at Link Between Certain Sunscreens, Endometriosis
11. Understanding the links between inflammation and chronic disease
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... ... Yisrayl Hawkins, Pastor and Overseer at The House of Yahweh, has released ... understood books in the Holy Scriptures, Revelation. The Book of Revelation paints a picture ... Many have tossed it off as mere rubbish, but Yisrayl Hawkins says that is ...
(Date:10/13/2017)... ... October 13, 2017 , ... “The Journey: From the Mountains ... possible to save lost souls in the Philippines. “The Journey: From the Mountains to ... dedicated teacher of the Bible. She has taught all ages and currently teaches a ...
(Date:10/12/2017)... ... 12, 2017 , ... CitiDent and San Francisco dentists, Dr. ... Oventus O2Vent technology. As many as 18 million Americans are estimated to suffer ... Oral appliances can offer significant relief to about 75 percent of people with ...
(Date:10/12/2017)... ... October 12, 2017 , ... IsoComforter, Inc. ( https://isocomforter.com ... the introduction of an innovative new design of the shoulder pad. The shoulder ... maximum comfort while controlling your pain while using cold therapy. By utilizing ice and ...
(Date:10/12/2017)... Maryland (PRWEB) , ... October 12, 2017 , ... ... magnetic drug delivery system that we intend to develop to enable prevention of ... can lead to severe hearing loss, especially in pediatric patients. For cisplatin, hearing ...
Breaking Medicine News(10 mins):
(Date:10/12/2017)... 2017   Divoti USA will engrave and ... standard of the latest FDA requirements, which stipulates new criteria regarding ... in need of Medical ID jewelry such as Medical ID Bracelets, ... engraved in terms of the new FDA requirements . ... Divoti offers this dark mark fiber ...
(Date:10/11/2017)... 11, 2017  Caris Life Sciences ® , a ... promise of precision medicine, today announced that St. Jude ... Oncology Alliance™ (POA) as its 17 th member. ... Jude Crosson Cancer Institute will help develop standards of ... tumor profiling, making cancer treatment more precise and effective. ...
(Date:10/10/2017)... ORANGE COUNTY, Calif. , Oct. 10, 2017  NDS received ... Mobile  — a medical-grade battery-powered display stand specifically designed for ... aims to transform technology into a clinical solution to support the ... costs. Innovative Design ... NDS ZeroWire Mobile Wireless Solution ...
Breaking Medicine Technology: