[Absolute bioavailability of beta-acetyldigoxin from tablets and drops in healthy subjects]. / Absolute Bioverfügbarkeit von beta-Acetyldigoxin aus Tabletten und Tropfen bei gesunden Probanden.

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.

Hemodynamic effects of brefanolol and propranolol assessed by noninvasive methods in patients with arterial hypertension.

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.

Pharmacokinetics of tocainide in patients with combined hepatic and renal dysfunction.

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.

[Reconstructive microsurgery in use of CO2-laser (author's transl)]. / Rekonstruktive Mikrochirurgie mit dem CO2-Laser.

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.

Prolonged action of drugs in rats with flavonoid-deficiency.

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.

Coumarin toxicity in different strains of mice.

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. These 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.

[A new experimental procedure of intraamniotic application of substances in multiparous experimental animals (author's transl)]. / Experimentelles Modell zur intraamnialen Applikation von Substanzen bei multiparen Versuchstieren.

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.

[Surgical refertilization by means of laser technic. Animal experimental study]. / Zur operativen Refertilisierung durch Laser-Technik. Tierexperimentelle Untersuchungen.

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.

[Animal experiment studies on the question of damage to the fetal kidney by gentamycin]. / Tierexperimentelle Untersuchungen zur Frage einer Schädigung der fetalen Niere durch Gentamyzin.

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.

[Influence of different obstetric-manipulations on the continuous measured pO2-tension upon the fetus sub partu (author's transl)]. / Einfluss unterschiedlicher geburtshilflicher Massnahmen auf die kontinuierlich gemessene pO2-Spannung des Feten sub partu.

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.

[Prevention and therapy of respiratory distress syndrome in premature infants by means of bromhexine metabolite VIII. Animal experimental studies on the therapeutic efficacy of bromhexine metabolite VIII in premature respiratory distress syndrome]. / Prophylaxe und Therapie des Atemnot-Syndroms bei Frühgebärenden mit Bromhexine Metabolit VIII. Tierexperimentelle Untersuchungen zur therapeutischen Wirksamkeit von Bromhexine Metabolit VIII beim Atemnotsyndrom Frühgeborener.

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.

[Intraamnial application of 14C-labeled lecithine at man 13 hrs. ante partum (author's transl)]. / Intraamniale Applikation von 14C-markiertem Lecithin beim Menschen 13 Stunden ante partum.

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.

[Continuous intrauterine pO2 determination in the fetus during birth]. / Intrauterine kontinuierliche pO2-Messung beim Feten unter der Geburt.

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.

Effect of xanthinol nicotinate treatment on platelet aggregation.

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.

[Intraamniotic application of lecithin in pregnant rabbits (author's transl)]. / Intraamniale Applikation von Lecithin bei hochträchtigen Kaninchen

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.

[Prevention and therapy of the respiratory distress syndrome in premature infants using lecithin. Distribution of 14C--labeled lecithin after intravenous and intraamnial administration in pregnant miniature pigs?]. / Prophylaxe und Therapie des Atemnot-Syndroms bei Frühgeborenen mit Lezithin. Verteilung von 14C-markiertem Lezithin nach intravenöser und intraamnialer Applikation beim graviden Zwergschwein

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.