In vitro and in vivo long term release of apomorphine from polymer matrices.

Since apomorphine actually reveals high efficacy in treatment of Parkinson's disease but only has a very short half life, it is of only limited clinical significance. To overcome this substantial disadvantage, drug application by long term delivery systems could be one possibility. Based on this background, ethylene vinyl acetate polymeric delivery systems were manufactured that differed in size, with either coated or uncoated surfaces, but were similar in apomorphine loading. Release from uncoated polymeric delivery systems followed first order kinetics, whereas coated polymeric delivery systems showed within the first 40 days a period of first order kinetics release, in which the release rate is approximately half that of the uncoated polymeric delivery systems, followed by a zero order kinetics release for more than 130 days with a daily release rate of 3.1 +/- 0.2 mg. In vivo release was investigated by determining plasma apomorphine concentrations after implanting polymeric delivery systems into the abdominal cavities of rats. Animals with uncoated polymeric delivery systems exhibited symptoms of an apomorphin overdosage within 20 days after surgery. Using coated polymeric delivery systems, a steady state plasma concentration of 15 ng/ml was observed, which was maintained over a period of 130 days after an initial period of high plasma concentrations. Based on our results, it is concluded that polymeric delivery systems might be an appropriate method for applying apomorphine for the treatment of Parkinson's disease.

[Cardiac sympathetic nerve activity in ischemic heart failure]. / Kardiale Sympathikusaktivität bei der ischämischen Herzinsuffizienz.

The prognosis in patients with heart failure, independent of etiology, is determined mainly by the extent of sympatho-adrenergic stimulation. In the development of heart failure sympathetic cardiac stimulation precedes systemic sympatho-adrenergic activation. Increased concentrations of the neurotransmitter norepinephrine can be found in the myocardium. This is a result of both increased release from sympathetic nerves as well as reduced neuronal reuptake. We were able to show that in advanced heart failure these effects are distributed heterogeneously in the heart. It has been shown experimentally that the effects on sympathetic neurotransmission are similar for both ischemia and heart failure. Therefore, these findings could indicate an important role of sympatholytic measures in patients with ischemia induced heart failure.

Uric acid lowering effect of oxipurinol sodium in hyperuricemic patients - therapeutic equivalence to allopurinol.

OBJECTIVE: Oxipurinol has been shown to be sufficiently absorbed after oral administration as a rapid release preparation of oxipurinol sodium. We compared the uric acid lowering affect of allopurinol and oxipurinol. METHODS: In a multicenter, randomized, double blind crossover trial in 99 hyperuricemic patients with normal renal function we investigated the uric acid lowering effect of oxipurinol sodium (O) in daily amounts equimolar to 300 mg allopurinol (A). Mean pretreatment plasma uric acid concentrations in groups A/O and O/A were 8.3 +/- 1.4 and 8.7 + /- 1.4 mg/dl, respectively. RESULTS: In group A/O the mean plasma uric acid decreased to 5.4 +/- 1.2 mg/dl with allopurinol treatment, and increased slightly to 5.7 + /- 1.3 mg/dl during the consecutive oxipurinol period. In group O/A plasma uric acid declined to 6.0 +/- 1.4 mg/dl with oxipurinol and was 5.6 + /- 1.3 mg/dl at the end of the allopurinol period. The overall average reduction compared to baseline was 3.0 mg/dl with allopurinol and 2.6 mg/dl with oxipurinol. The difference between the 2 treatments was small but significant (multiple p=0.027,2 tailed). The corresponding mean plasma oxipurinol concentrations were 9.24 mu g/dl at the end of the allopurinol period and 9.9 mu g/dl after treatment with oxipurinol (NS). CONCLUSION: Oxipurinol is well absorbed and sufficiently effective in hyperuricemic patients when administered as a rapid release preparation of oxipurinol sodium. Oxipurinol sodium could be a substitute for allopurinol in hyperuricemic patients and possibly also with new uses for allopurinol.

[Long-term treatment of hyperlipoproteinemia with etofibrate]. / Langzeitbehandlung von Hyperlipoproteinämien mit Etofibrat.

In the treatment of hyperlipoproteinemia, longterm results are of particular interest. Fifty-five patients with mixed hyperlipidemia, who had been treated with Etofibrat in a controlled clinical trial, underwent a follow-up examination one year after conclusion of the study, and data of current lipid treatment and lipid status were recorded. Also investigated were the compliance and motivation of the patients. Within the course of the clinical study, patients with combined hyperlipidemia showed a marked decrease in cholesterol levels of 21%, and of triglycerides of 38%. At the end of the trial, 20 patients continued to receive Etofibrat. Under this treatment, the lowered cholesterol and triglyceride levels were maintained, while in patients receiving other lipid-lowering agents, the triglycerides rose again, and patients not receiving any further medication showed an increase in both triglyceride and cholesterol levels.