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Biomedical subjects

H Nowak

Publications and source records attributed to H Nowak.

At least 91 records · Page 5Linked to original sources
PubMed1982

Sucralfate: pharmacokinetics, metabolism and selective binding to experimental gastric and duodenal ulcers in animals.

Pharmacokinetics, metabolism, and binding capability of a basic aluminium salt of sucrose octasulphate (sucralfate, Ulcogant) to ulcer lesions were investigated in Wistar rat, Beagle dog, Rhesus, and Cynomolgus monkey with 14C-labelled material. After i.v. injection in rats the 14C-radioactivity has a very short serum half-life of 1 h and is excreted almost completely by the kidneys. After oral administration only a very small portion of the dose is detectable in serum which is eliminated rapidly from the intravascular space. From the renal excretion data it is concluded that sucralfate is absorbed from the gastrointestinal tract of rat, Beagle dog, and Rhesus monkey only from 1% to 5% of the dose. The radioactive constituents in plasma, urine, and feces of rat and Cynomolgus monkey were analysed by HPLC. Both after i.v. and p.o. administration only unchanged substance could be detected. A possible binding of 14C-sucralfate to the ulcerated mucosa of stomach and duodenum was investigated in rats by histoautoradiography. The ulcers were induced by acetic acid. A selective accumulation of 14C-sucralfate in the area of the stomach ulcer could be demonstrated as long as 8 h after single p.o. administration. In the duodenum the autoradiographs showed a specific binding of 14C-sucralfate to the ulcerated mucosa at 1, 2, and 4 h after administration. Neither pretreatment with an H2-receptor antagonist nor simultaneous administration of an antacid influenced the binding of 14C-sucralfate. These results suggest that the mode of action of sucralfate is the formation of a protective layer which stops harmful agents like gastric juice and bile from further damaging the ulcerous lesions, thus ensuring an uninterrupted healing process. The very small extent of absorption and the rapid excretion from the organism minimize the risk of a systemic burden.

Aluminum↗
PubMed1979

[On the existence of a myeloproliferative factor in patients with a myeloproliferative syndrome (author's transl)].

Serum of patients suffering from a chronic myeloproliferative disorder (polycythaemia, era, osteomyelofibrosis, chronic myeloid leukaemia) and serum of lethally irradiated rats injected before application of a single doses of erythropoietin did not enhance the effect of erythropoietin -- measured with the iron incorporation rate of polycythemic mice. The rationale for these experiments is to try to find a "myeloproliferative factor", which augments the number of stem cells as described in sera of patients with polycythaemia vera, osteomyelofibrosis, and lethally irradiated mice.

Adult↗
PubMed1978

Clinical pharmacology in normal volunteers of praziquantel, a new drug against schistosomes and cestodes. An example of a complex study covering both tolerance and pharmacokinetics.

The tolerance of Praziquantel (2-cyclohexylcarbonyl-1, 3, 4, 6, 7, 11b-hexahydro-2H-pyrazino-[2, 1-a]isoquinoline-4-one) in oral doses of 1 X 20 mg/kg, 1 X 50 mg/kg, 3 X 10 mg/kg and 3 X 25 mg/kg body weight (tau = 4 h) was tested in a complex study involving 36 healthy volunteers. In addition to the usual assessment of clinical chemistry, haematology, coagulation physiology, urinalysis, clinico-physiological examination including EEG, and medical examination, clinico-psychological parameters were also recorded and special neurological investigations were performed. No clinically relevant changes were found in any of the laboratory parameters, nor in the medical-neurological or clinico-physiological examinations. Based on a few clinico-psychological parameters and subjective comments, the largest daily dose tested (3 X 25 mg/kg = 75 mg/kg) produced a slight, transient disturbance in general well-being, which was barely detectable on objective clinical examination. The pharmacokinetic behaviour was dominated by rapid metabolism and pronounced first-pass metabolism of praziquantel, which greatly limits the value of results obtained by GC analysis of unchanged drug in serum. The peak concentration in serum was reached after 1--2 h, and the elimination half-life for the period 2--8 h was 1--1.5 h.

Adult↗
PubMed1978

Comparative bioavailability: influence of various diets on the bioavailability of indomethacin.

After oral application of 100 mg indomethacin to eight healthy male volunteers, the concentrations in plasma and their time course were determined when the drug was given to fasting individuals or after a high-protein, a high-lipid or a high-carbohydrate meal. The study was designed as a fourfold-crossover experiement with intermissions of at least one week between applications. Indomethacin in plasma was determined by fluorimetry after a double extraction procedure. Indomethacin plasma concentrations and the truncated areas under the curves (AUC) were evaluated. Administration to fasting subjects provides higher plasma levels and a smaller tmax value than after either one of the three diets. Also the absorption rate was higher in fasting individuals. However, the absorbed amount of indomethacin after 24 hr was practically equal in all four groups. Attempts to distinguish between the effects of the various diets revealed significant differences in the time period necessary to reach the peak values. After high-protein and high-lipid diets they were reached in the 90 min sample while after high-carbohydrate 120 min were required. These values are significantly different from fasting controls (45 min) and from each other. There is no great influence of food on the other aspect of bioavailability, amount of unchanged drug reaching the systemic circulation.

Adult↗
PubMed1977

[Psychodynamic aspects of paraphrenia].

Proceeding from Kraeplin's original a brief summary is given of the literature about the extensive interpretations of the term paraphrenia. Our study is based on a catamnestic examination of schizophrenic diseases first acute in 1930-1940 after 30 respectively 40 years (H. Hinterhuber) and a second group of paraphrenics who at the time being have been under our control for five years. By a simplifying scheme our own conception of paraphrenia is then defined and differentiated from the paranoid schizophrenia and the development of paranoia with special reference to the characteristic juxaposition of schizophrenic symptomatic in otherwise intact personality without a noteworthy derangement of the evironmental relations. The intact personality stands in clear contrast to the only "intact outside personality' with schizophrenic derangement of the ego. Thus the paraphrenic has the possibility to withdraw to the core of his sound personality and erect a mostly stable barrier against the partly massive hallucinations on the periphery of his personality. This corresponds to a passive attitude of avoidance in the sense of behaviour psychology. As THEREFORE the paraphrenic, similar to the phobic, tends to confine the borders of his existence by an increasingly passive avoidance attitude, he tries by a systematic desensibilisation to keep the borders of existence just in the area between psychosis and sound personality and thus render the best possible extent of personality development avoiding secondary restrictions.

Behavior Therapy↗
PubMed1976

[Pharmacokinetics of pramiverine in rats, dogs, and monkeys (author's transl)].

The pharmacokinetic properties of 4,4-diphenyl-N-isopropyl-cyclohexylamine-hydrochloride (pramiverine, Sistalgin) in Wistar rats, beagles, and rhesus monkeys are described. After i.v. injection of 14C-labelled pramiverine incorporation of radioactivity from the blood into organs and tissues is rapid. The radioactivity is eliminated from the blood with a half-life of 4-7 h in rats, 17-32 in dogs, and 8-26 h in rhesus monkeys. Unmetabolized pramiverine, in contrast, is eliminated much faster, the half-lives are 2 h in dogs and 3 h in rhesus monkeys. After oral administration maximum serum concentrations are reached after 4 h in rats and dogs and 2 h in rhesus monkeys. The drug undergoes a marked first-pass effect in the liver. In all species pramiverine is absorbed rapidly from the gastro-intestinal tract. Drug and/or metabolites are eliminated in rats and dogs predominantly with feces, in monkeys with urine, independent of the route of administration. During a 6 h interval, biliary elimination was found to be 50% after i.v. and 30% after oral administration. 90% of pramiverine present in the blood plasma is reversibly bound to proteins.

Administration, Oral↗
PubMed1976

[Metabolism of pramiverine (author's transl)].

The metabolite patterns of 4,4-diphenyl-N-isopropyl-cyclohexylamine-hydrochloride (pramiverine, Sistalgin) in urine, feces, bile and serum of Wistar rats, beagle dogs, rhesus monkey and man were analyzed with radio thin-layer chromatographic techniques. The structures of six pramiverine metabolites were elucidated. Pramiverine is eliminated unchanged in only minute amounts via the renal, the biliary and the fecal route. Consequently an almost quantitative absorption and metabolism takes place. Metabolite patterns in serum and urine differ considerably indicating that some of the metabolites are excreted preferentially by the kidney while others are reabsorbed to various degrees. The identified metabolites are products of dealkylation, deamination and hydroxylation reactions.

Animals↗
PubMed1976

[The influence of mepiprazol on monoamine metabolism in the rat CNS: demonstration of reduced norepinephrine activity and simultaneously enhanced serotonin and dopamine activities (author's transl)].

Biochemical studies of monamine turnover and neuronal reuptake indicate that mepiprazole, a novel psychotropic pyrazole derivative, decreases norepinephrine receptor activity and enhances serotonin and to a lower extent also dopamine activity in the rat CNS. It can be concluded that mepiprazole might be of value in the treatment of certain types of depression and might be helpful to alleviate side effects of L-dopa in the treatment of parkinsonism.

Animals↗