Single dose pharmacokinetics of fendiline in humans.

Fendiline was administered intravenously (3 mg) and orally (50 mg and 75 mg) in a cross-over study to six healthy volunteers. The plasma levels of unchanged fendiline and of total radioactivity were measured. Fendiline was absorbed well and its concentration declined biexponentially with mean terminal half-lives of 20-35 h. Since the drug is extensively metabolized, only 12% of total radioactivity in plasma corresponded to fendiline in the case of intravenous administration as compared to less than 2% after oral administration. 56-65% of the administered dose are excreted via the urine and 18-25% with the feces within five days.

Visually evoked potentials in cortical and subcortical brain structures of conscious rabbits with chronically implanted electrodes. Standardized normal values and the influence of some psychopharmacological agents on them.

By means of a modified and simplified surgical and implantation technique, standardized values for visually evoked potentials (EP) from 7 brain structures (caudate nucleus, posterior hypothalamus, mesencephalic reticular formation, intra-laminar thalamic nuclei, amygdala, dorsal hippocampus and visual cortex) are obtained. The importance of a careful selection of the animal material, constant test conditions and the selection of test parameters as a prerequisite for the assessment of psychotropic drugs is emphasized and discussed. As an example of the specific influence on visually evoked potentials in the above named brain structures, the effects of haloperidol and amytriptyline on latencies and amplitudes of the individual parameters of EPs are described. It is assumed that the method described can be of great assistance for investigation and classification of newly developed substances.

Classification of psychoactive drugs by visually evoked potentials in rabbits by means of multiple discriminant analysis. A possible way of predicting the clinical efficacy of new psychoactive drugs.

The influence of representatives of various groups of antipsychotic drugs on the visually evoked potential (EP) was investigated with the aid of a modified recording and evaluation technique for the rabbit EEG from cortical and subcortical structures. The starting point was the hypothesis that changes in the EP in animal experiments caused by representative members of these "substance groups" (neuroleptics with predominantly antipsychotic or predominantly sedative effect, and antidepressants with predominantly mood-brightening or predominantly sedative main components) make predictions of the clinical efficacy of "unknown" substances possible on the basis of clinical therapeutic principles of classification. Experiments were carried out with haloperidol and fluphenazine, chlorpromazine, amitriptyline and doxepin, and with imipramine and clomipramine, as representatives of these classes of substances. The hypothesis was checked by attempts to assign amitriptyline and chlorprothixene in varying dosage, haloperidol, benzperidol and mianserine to appropriate classes. As classification and assignment procedure we used stepwise multiple discriminant analysis (SWDA) according to our modification of the BMD 0 7 M Program. The purpose of the latter program, and its applicability to our studies, are described and discussed. It was found 1. that with EP data from animal experiments it is possible to classify various groups of psychoactive drugs on the basis of clinical therapeutic findings, using SWDA; 2. that assignment of "unknown" compounds can be based on this classification; 3. that hence with some caution predictions of the clinical effect of newly developed substances may be made on the basis of findings in animal experiments. The EP variables which contain most information for making up the separation formula and hence are of special importance, are investigated with respect to their possible neurophysiological evidential value, and their significance is discussed. It was found that the EP from the visual cortex are of particular significance for the separation of groups in the form presented here.

[Bioequivalence of phenylbutazone preparations following a single intramuscular administration]. / Bioäquivalenz von Phenylbutazon-Präparaten nach einmaliger intramuskulärer Applikation.

Bioequivalence was estimated in 6 resp. 7 male volunteers for two combination drugs of phenylbutazone (Neuro-Elmedal, Sigma Elmedal) after intramuscular administration using a monopreparation as a standard. Plasma levels of phenylbutazone were assayed by high pressure liquid chromatography. With respect to rate and extent both combination drugs were identical to the mono drug.