EVIDENCE OF PHARMACOKINETIC-PHARMACODYNAMIC RELATIONSHIPS BY MEANS OFPHARMACO-EEG IN HEALTHY-VOLUNTEERS FOLLOWING ADMINISTRATION OF CYCLANDELATE

In an open randomized cross-over study 800 mg cyclandelate (Natil(R), CAS 456-59-7) was applicated to 24 young, male volunteers. Before and during 24 h after application of a single dose a 17-channel, quantitat ive topographical pharmaco-EEG was recorded A significant increase of the spectral power density was observed in the alpha(2), beta(1) and b eta(2) frequency bands starting 2 h after application until 4.5 h. The increase in beta(1) and beta(2) power was observed in the parietocent ral area of the cortex. The difference between the circadian developme nt of the EEG power and the development after medication was obvious a fter 3 until 4.5 h. For the beta frequencies only a weak statistical c onfirmation could be observed, but for the alpha(2) frequency a signif icant difference between the circadian and the EEG power under cycland elate was found using the sign test. Altogether a quantitative effect on brain activity was detected after oral application of cyclandelate, reaching its maximum before the blood concentration of the metabolite s cyclandic glucuronide and mandelic acid reached their peak heights.