Therapeutic efficacy of vincamine in dementia.

This trial was performed to investigate the therapeutic efficacy of vincamine in the treatment of primary degenerative and vascular dementia. 152 male and female patients aged between 50 and 85 years from two psychogeriatric centers and two nursing homes were initially included in the trial and screened for eligibility. 142 patients completed the trial. Clinical diagnosis was established according to DSM-III-R criteria. Allocation of the patients to the primary degenerative dementia of the Alzheimer type (DAT) group or the multi-infarct dementia (MID) group was based on computed tomography scans, electroencephalographic findings and the Hachinski Ischemic Score. In a 12-week double-blind treatment either 30 mg vincamine or placebo was given twice daily. Confirmatory statistics included item 2 of the Clinical Global Impression (CGI), the total score of the Sandoz Clinical Assessment Geriatric (SCAG) scale, the subscale 'need for help' of the nurse's rating of geriatric patients (Beurteilungsskala für geriatrische Patienten; BGP) and the total score of the Short Cognitive Performance Test (Syndrom-Kurztest; SKT). In addition, data on tolerance and on therapy response were evaluated based on descriptive statistics. The therapeutic efficacy of vincamine was clearly demonstrated by confirmatory analysis as the drug was statistically significantly superior to placebo in all four target variables. The clinical relevance of the outcome was further underlined by the results of the responder analysis of the variables SCAG, BGP and SKT. Based on the results of this trial, it can be accepted that the therapeutic effect of vincamine is superior to placebo in patients with mild to moderate dementia of degenerative and vascular etiologies.

[Comparative studies on the in vitro dissolution and bioavailability of various acetylsalicylic acid preparations]. / Vergleichende Untersuchungen zur In-vitro-Freisetzung und Bioverfügbarkeit von verschiedenen Acetylsalicylsäure-Fertigarzneimitteln.

For five different brands of acetylsalicylic acid (ASA) preparations the in vitro/in vivo data were determined and tested for comparability. The in vitro dissolution rates were determined by two different methods (Paddle, rotating basket) whereas the in vivo data were obtained from 15 volunteers in a 5-fold cross-over trial. The markedly worse in vitro dissolution (rotating basket) of one preparation is in contrast to the in vivo data which showed bioequivalency of all five preparations. It is doubled that in vitro measurements alone reveal sufficient informations for any predictions of the in vivo characteristics (e.g. bioavailability) of a preparation. It was possible to determine separately ASA and salicylic acid using a highly selective HPLC-method developed by us.

[Comparative study of the bioavailability and the pharmacodynamic effect of five allopurinol preparations (author's transl)]. / Vergleichende Prüfung der Bioverfügbarkeit und des pharmakodynamischen Effektes von fünf Allopurinol-Zubereitungen.

The aim of this study was to determine the relative bioavailability of five oral allopurinol preparations and evaluation of the pharmacodynamic effect. Included were two slow-release formulations. The study was performed as complete five-way randomized steady-state cross-over trial in 10 healthy volunteers. Each day 300 mg of 1H-pyrazolo-(3,4-d) pyrimidin-4-ol (allopurinol) were orally administered for 7 days, followed by a wash-out phase of 14 days. The minimal serum levels of allopurinol and its major metabolite oxypurinol were determined by HPLC. In parallel the concentrations of uric acid in blood and in 24-h urine were measured. The two slow-release formulations had a significantly lower relative bioavailability compared to the normal formulations and, moreover, a slow-release effect could not be demonstrated. In all cases the clinical effect of the test preparations could be demonstrated, and a correlation between bioavailability and pharmacodynamic effect could be calculated. A correlation between published in vitro data and the present in vivo data could not be found.

[Study of the effect of a dexamethasone-containing antirheumatic on the hypothalomus-adenohypophysis-adrenocortical system]. / Prüfung der Wirkung eines Dexamethason-haltigen Antirheumatikums auf das Hypothalamus-Hypophysenvorderlappen-Nebennierenrinden-System.

The aim of this study was to investigate the effect of an analgesic-antirheumatic fixed combination drug containing dexamethasone (Ambene) on this endocrine system. 10 healthy volunteers received an intramuscular injection of Ambene as either single dose once, single dose on three consecutive days or on three alternating days. Early morning ACTH plasma concentrations, endogenous cortisol profiles and dexamethasone kinetics were determined and insulin-hypoglycemia tests stimulated stress conditions before, during and after Ambene-application. In all cases treatment led to short-term suppression of the reactability of the Hypothalamus-Anteropituitary Corticoadrenal System. Three days after single dose or alternating day administration for three days reactions of this endocrine system were completely restored, while after administration on three consecutive days there still was a slight decrease in basal and insulin-stimulated cortisol values. The short half-life of water soluble dexamethasone in Ambene appears to be the reason for the rapid restitution of this endocrine system.

[On the question of endocrine side effects in patients on medication for renal calcium stone disease (author's transl)]. / Zur Frage endokriner Nebenwirkungen bei der medikamentösen Prophylaxe calciumhaltiger Harnsteine.

In patients with recurrent idiopathic nephrolithiasis we studied whether treatment with sodium cellulose phosphate leading to decreased intestinal calcium absorption could induce secondary hyperparathyroidism and whether thiazides which diminish calciuria would impair glucose tolerance. After removal of a actual kidney stone, 74 patients were treated for one year as follows: 25 (group 1) received conventional therapy (Nieron), 22 (group 2) received sodium cellulose phosphate, and 27 (group 3) received sodium cellulose phosphate plus hydrochlorothiazide. The period of one year was too short to evaluate the effectiveness of treatment regarding stone recurrence, however, a significant decrease in calciuria only was seen in group 3. With respect to the possibility to develop secondary hyperparathyroidism, group 2 and group 3 did not reveal any hints. In group 3, the thiazide treatment did not worsen glucose tolerance. Therefore, longer lasting studies with these drugs could be performed without evident danger to develop the mentioned side effects.

[Comparison of methods of determination of serum doxycyline assessing relative bioavailability of two commercial formulations (author's transl)]. / Vergleich der Messmethoden von Doxycyclin im Serum bei einer Prüfung der relativen Bioverfügbarkeit zweier Handelspräparate.

The present study was undertaken to evaluate the accuracy of the analytical results of an investigation of relative bioavailability of two doxycycline preparations. Six methods in four laboratories were applied: one fluorimetric, three high-pressure-liquid-chromatographic and three microbiological methods. The analyses were performed after coding the samples. In all cases the two preparations were bioequivalent. When comparing the methods, it could be shown that the fluorimetric method was slightly more accurate than the others. The HPLC-methods were almost as accurate. The results of the microbiological determinations showed the lowest accuracy. Two of the results were in good agreement with the biochemical methods, whereas the third showed such a high deviation that a comparison was no longer possible. Altogether a good agreement of all compared methods (except one) could be demonstrated.