Measurement of drug-ethanol interactions

Usefulness of the methods

The majority of ambulant patients taking drugs consume relevant amounts of alcohol. As these patients often cannot manage without driving cars or operating dangerous machinery, testing of drug-ethanol interactions is of great social importance and remains a significant topic in the process of drug approval by the health authorities world-wide. Synergistic as well as antagonistic (e.g. of serotonin re-uptake inhibitors) interactions can be observed.

Principle of the methods

Administration of ethanol:
Ethanol is given by intravenous infusion. This results in blood ethanol concentrations with low inter individual variation in contrast to the oral admi- nistration. Continuous monitoring over the whole test period is carried out by measurement of the breath ethanol concentration.

Measurements:
We have designed a system of multidimensional tests which are able to assess the multitude of cerebral dysfunctions which are usually initiated by intake of alcohol. These tests are presented in detail on the reverse of this page.

Reference data

Data are available for antidepressants, benzodia -zepine and non-bezodiazepine type of anxiolytics, surfactants, H2-blockers and proton pump inhibitors.

Advantages of the methods

The test systems:
Car driving simulators - which satisfactorily mimic the demands of driving in traffic - are mostly too complex and also subject to motivational and learning effects, which complicate their evaluation. Therefore, in our experimental setting, a pursuit tracking test which measures eye-hand coordination as required for car driving is combined with the ODT (Oculodynamic Test, testing the saccadic eye movements) which has the outstanding feature that there is no influence of motivation and learning.

Administration of ethanol:
Oral administration of ethanol, due to tremendous differences in velocity and quantity of absorption, results in erratic influences on performance. Therefore in our experiments ethanol is given by intravenous infusion, to assure absolute bioavailability of ethanol (or exact titration of BAC).

Options

• Evidence/ exclusion of pharmacodynamic interactions of drugs primarily acting on the CNS with ethanol
  (e.g. antidepressants, antiepileptics, anxiolytics)
• Evidence/ exclusion of pd-interactions with ethanol of drugs potentially acting on the CNS as a side effect (e.g. antihypertensives, spasmolytics, NSAIDs, hypolipemics, H2-blockers,. proton pump inhibitors)
• Evidence of an antagonism to the ethanol effect on performance (e.g. of serotonin re-uptake inhibitors)
• Concomitant pharmacokinetics