Psycho- and immunopharmacological factors relevant to selection of volunteers in clinical studies

There are many well-known factors and variables which play a role in the ev aluation of pharmacokinetic and pharmacodynamic results gained from healthy volunteers. The genetic constitution is influenced by age, sex, circadian and seasonal variations, dietary factors, immunological function, alcohol i ntake, smoking, etc. Vesell repeatedly pointed out these facts some time ag o [Vesell 1982, Vesell and Passananti 1977]. Since Janke [1964], we have su spected that personality traits can also influence the drug response. The f ollowing overview is dedicated to this field designated as differential psy chopharmacology which, from the point of view of the author, has been given too little attention by pharmacologists and clinical pharmacologists. It h as been demonstrated that the effect of psychotropic drugs, including place bo, can be differentially influenced by personality traits, e.g. introversi on/extroversion, high level neuroticism/ low level neuroticism and success motivation/failure motivation. For example, relatively high doses of diazep am (0.3 mg/kg), when compared to placebo, only impaired the psychophysical performance of extroverted volunteers whereas introverted volunteers remain ed unaffected. Pharmacokinetic parameters, e.g. absorption, biotransformati on, can also be affected by the level of neuroticism or by anxiety, as demo nstrated for diazepam, caffeine, paracetamol and theophylline. The absorpti on kinetics of diazepam and caffeine clearly differ between volunteers with high neuroticism scores and those with low neuroticism scores. Emotionally unstable volunteers absorbed the substances more quickly and more complete ly than emotionally stable volunteers. There were surprising differences in various immunological indices between dominant and submissive subjects. In dominant volunteers the immune system was more activated than in submissiv e volunteers. In the future, it will become increasingly necessary to obtai n results for such target groups and to avoid generalized data, which may c onceal the actual events. Differential clinical psycho-neuro-immunopharmaco logy may be an approach which is helpful in the development or "volunteer m odels" for clinical research in Phase I.