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In a crossover design in random order 12 healthy male volunteers were given either beta-acetyldigoxin (Novodigal, CAS 5511-98-8) tablets, oral solution or i.v. application at a digoxin equivalent dose of 0.284 mg. To reach steady state each preparation was given for 10 days on a once-daily schedule. On days 8, 9 and 10 of each observation period blood was sampled to determine trough concentrations of digoxin in steady state. In addition, on day 10 blood was collected repeatedly at appropriate time intervals and urine was sampled concomitantly for 24 h. Trough values during steady state and 24 h AUC were used to calculate digoxin bioavailability for tablets and oral solution. From trough values, the mean bioavailability for beta-acetyldigoxin tablets was 91.2% (range 73.1-118.1) and for solution 93.8% (range 65.7-114.8). Using the AUCs 0-24 h at steady state bioavailability was calculated 77.7% for the tablets and 84.5% for the solution. Since trough values in steady state represent the body burden of digoxin which is supposed responsible for the therapeutic effect, trough values should be given priority for the determination of digoxin bioavailability from beta-acetyldigoxin tablets and solution. All formulations were well tolerated. No clinically relevant side effects were observed.

In a placebo-controlled, randomized, cross-over study, 16 patients (10 males, 6 females; 50.6 +/- 10.4 years; body weight of 74.5 +/- 8.9 kg; mean +/- SD) with arterial hypertension (WHO stages I and II) were administered single oral doses of placebo, 80 mg of propranolol, as well as 50 and 100 mg of brefanolol (a beta-adrenergic blocking agent with vasodilating properties) in order to determine the resulting hemodynamic effects. Blood pressure, heart rate, and various hemodynamic parameters were assessed noninvasively by mechano- and impedance cardiography as well as by venous occlusion plethysmography before and 2, 4, 6, 10, and 24 h after drug administration. Treatment with propranolol resulted in the typical hemodynamic changes induced by a beta-adrenergic blocking agent characterized by a significant reduction in blood pressure, heart rate, cardiac output, stroke volume, and an increase in total peripheral resistance. A dose of 100 mg of brefanolol also led to comparable hemodynamic effects. Similar significant decreases in blood pressure, heart rate, and cardiac output also occurred with 50 mg of brefanolol, but stroke volume and reactive hyperemia increased. Thus, in this phase of drug development, dose titration with 50 and 100 mg of brefanolol indicates that the lower dose gives rise to a more balanced relationship between its beta-adrenergic blocking and vasodilating properties.

Inhalt: Aufgrund der morphologischen Beschaffenheit des Genitaltraktes bei der Sau ist eine Beobachtung der Cervix uteri mit gewissen Schwierigkeiten verbunden. Die vorliegende Untersuchung hatte zum Ziel, die mittels Scheidenspekulum vor und nach der Geburt erkennbaren Veranderungen des Zervixkanals zu beschreiben. Contents: The cervix uteri in sows at parturition. Due to its unique morphology observations on the uterine cervix of the pig are relatively rare. The present investigation consists of a description of the gross cervical changes observed by way of a vaginal speculum before and after parturition.

Animal experiments on rabbits with a CO2 laser concerning end-to-end-anastomosis of cornua uteri are reported. The rate of success of this laser technique by a before investigated optimal energy density of 64 Watt sec/cm2 (8 Watt,0,2 sec) was about 70% deliveries without any complication. This method could be an alternative to the presently used microsurgical methods of refertilisation in human tubar sterility.

Because of the clinical and biochemical state of a 26 years old patient an erythroblastosis was expected. Continuous controls revealed that delivery in the 36th week of pregnancy was necessary. A therapeutic research with lecithine through the maternal circulation in this special case was carried out in order to prevent a respiratory distress syndrome of the premature infant.

A study about continuous intrauterine pO2-measurement of the human fetus sub partu. It is reported about a continuous intrauterine unbloody pO2-measurement of the human fetus sub partu. There was found a good correlation in different cardiotocographic patterns between labour, fetal heart frequency and pO2-registration.

The aim of our researches was to point out a new therapeutical possibility to prevent a respiratory distress syndrome of prematures by application of 14C-lecithine. The experiments were carried out at Göttinger mini-pigs. Examining the placental passage it could be determined that an intravenous application was not efficient, while after intraamnial application of lecithine a rapid resorption in the fetal organism was proved. Of special interest was a high accumulation of lecithine in the fetal lung-tissue. These results indicate a possible therapeutical way to prevent a respiratory distress syndrome by lecithine substitution.

In preparing a clinical study 14C-labelled bromhexine metabolite VIII was applied intraamnially in animal experiments. The distribution was measured in different maternal and fetal organs by thinlayer chromatography and autoradiography. A complete placental passage was found in both directions. An organspecific accumulation in the fetal lungs could not be demonstrated.

It was examined, whether by intraamnial applicated lecithine an approaching respiratory distress syndrome could be prevented. This possibility of therapy was tested on a fetus unviable of life. It was shown by examining the lavage-fluid of the fetal lung, as well as the organ homogenates of lung; liver and gut, that the intraamnial applicated lecithine was metabolised and resynthesised in the organism. In the lung the lecithine was present as a complete molecule.

A report of a 36 year old patient is given who was hospitalized because of an erythroblastosis. An indicated sectio caesarea resulted in an intraamnial application of lecithine for preventing a respiratory distress syndrome. It can be concluded by the measured lecithin-concentration that a high phospholipid-level in the amniotic fluid leads to an increased resorption by the fetus. Postpartal investigations showed a completely normal lung function in the newborne.

The disposition of tocainide following an i.v. infusion of tocainide HCl 100 mg was studied in 6 patients with decompensated cirrhosis (ascites) and renal dysfunction. In one patient with active hepatic necrosis the terminal plasma half-life was 57.4, and in the others the half life ranged from 16.0 to 29.0 h. The increase in half-life was correlated with biochemical evidence of renal dysfunction, but not with individual tests of hepatic function. Non-renal clearance of tocainide was similar to values reported previously in healthy subjects and patients with acute myocardial infarction. The apparent volume of distribution of tocainide was increased and the pattern of distribution was abnormal in some patients, as plasma concentrations increased after an initial fall and the elevated concentrations then persisted for several hours. This abnormality appeared to be most marked in patients with the greatest degree of liver dysfunction.

Treatment of 24 male patients with 3 g/day of xanthinol nicotinate did not change the in vitro measurements of ADP-induced platelet aggregation but produced a marked inhibition of collagen-induced platelet aggregation. This effect may be connected with the drug-induced depression of the ATP level in platelet-rich plasma. Changes in the platelets in the patients' blood or in the lipid composition and the concentration of uric acid in their serum were ruled out as reasons for the decrease of the collagen-induced aggregation. The activity of the three serum enzymes y-GT, GOT, and GPT and the concentration of the blood sugar did not change.

As coumarin is used as flavouring agent for human food as well in the treatment of angiological diseases toxic and — in rats — even cancer-ogenic effects of the drug should be considered carefully. However, since in rats its metabolism results mainly in hydroxyphenylcarbonic acids but in man mainly in 7-hydroxycoumarin, the rat seems to be unsuitable for studies related to coumarin side effects in man. Therefore the toxicity of coumarin was studied in DBA/2J-mice, having high coumarin-hydroxylase activity in the liver as man, and CH3/HeJ-mice, having low activity as rats. The LD50 of orally administered olive oil dissolved coumarin was found to be double as high in male DBA- than in male CH3-mice (780 and 420 mg/kg; parallel dose effect curves). The oral administration of 350 mg/kg coumarin increased the serum GOT and SDH in CH3-mice to higher levels than in the other strain. Up to 32 weeks feeding with 0.5 and even 1.0% of coumarin in standard diet was tolerated without any impairment of the mice’s attitude and growth. 10, 20 and 32 weeks administration of 0.5% coumarin in the diet did not have any effect on the serum levels of GOT, ɣ-GT and SDH. 1.0% of coumarin, i.e. up to 2 g/kg·day, caused only minimal and irregular increases of one or two enzymes. However, light and — as far as done — electron microscopy did not reveal any consequences in direction to coumarin caused liver damage. — Careful and previous extrapolation of these results to man does not exhibit any important risk of coumarin containing foodstuffs or remedies.

CO2-Laser is presented for application in reconstructive operations. At cornua uteri and urine bladders of rabbits excisions were undertaken. The free wound edges were approximated and coagulated by laser irradiation. After these operations 70% (uterus) respectively 90% (urine bladder) of the organs remained fully functionable.

In rats the hexobarbital metabolism is impaired after different surgical procedures leading to muscle damage. This leads to a prolongation of the hexobarbital action. The prolonged effect of hexobarbital in rats with lymphostatic encephalopathy is considered an unspecific consequence of the tissue damage during lymphectomy.

It is reported about animal experiments of pregnant guinea pig. We found a special affinity of gentamyzin to maternal and fetal kidney-tissue. The application of this aminoglycosid seems therefore problematic in pregnancy.

The influence of different obstetric-manipulations and medicamental applications was investigated in regard of the continuous measured fetal intrauterine pO2-tension sub partu. By demonstrating some original registrations it was intended to point out the efficiency of these obstetric-manipulations.

The general toxic effects of coumarin, as well as coumarin hepatotoxicity were found to be less in DBA/2J mice than in CH3/HeJ mice. Thess results are discussed in the context of a strain-specific coumarin metabolism and indicate the need for suitable animal models to assess the toxicity of a given substance in man.

In order to find possibilities to influence therapeutically the respiratory distress syndrom at the premature infant animal experiences were carried out with 14C-lecithine. High pregnant rabbits got 14C-lecithine by intraamnial application. Investigation of the distribution of lecithine in the amniotic fluid and in the fetal organism showed an accumulation of lecithine metabolits in lung and lever tissue.

In rats, pretreatment with caffeine or ethanol shortens the duration of the harmine tremor and decreases the brain concentrations of this alkaloid. Caffeine and ethanol do not influence the plasma concentration of harmine, its plasma protein binding and its cerebral concentration at the termination of the tremor. The findings are regarded as indicative of a reduction by caffeine and ethanol of the blood-brain barrier permeability to harmine.

In order to proof the distribution and metabolizing of various substances experimental operation models in animals were developed. The placental transfer was examined in guinea pigs and rabbits; while metabolism was studied in the Göttinger miniature pig. The presented model enables us to examine the following compartments: maternal organism, placenta, amniotic fluid and fetus.

In flavonoid-deficient rats, hexobarbital-sleeping times are prolonged. The hexobarbital concentrations in brain, liver and plasma are increased. These results are discussed as a consequence of an impaired drug metabolism.

In flavonoid-deficient Wistar-rats, the action of caffeine, harmine, hexobarbital, morphine and pentobarbital is enhanced. In contrast, the thiopental sleeping time is shortened. These observations may indicate impaired drug metabolism as a consequence of the flavonoid-deficiency state.