Influence of H2-receptor- and proton pump inhibitors on some functions of the oxydative and conjugative drug metabolism.

There are numerous investigations describing the influence of histamine H2-receptor antagonists and proton pump inhibitors on cytochrome P450-mediated hepatic oxydative and conjugative drug metabolizing enzymes. The aim of this study was to investigate the influence of the H2-receptor blockers cimetidine, ranitidine, famotidine, nizatidine and of the proton pump inhibitors omeprazole and lansoprazole on the acetylation capacity and on different microsomal monooxygenases of the rat liver. The experiments were performed in two randomized studies with male Wistar rats after a 7-day pretreatment of the animals with antisecretory, equipotent doses of the investigational products.

Effects of nocloprost clathrate on absorption of acetylsalicylic acid.

The cytoprotective prostaglandin E2 analog nocloprost clathrate (NOCLO) is tested as a prophylactic for gastrointestinal lesions of NSAID. The effects of 400 micrograms NOCLO versus respective placebos with and without equivalent amounts of beta-cyclodextrin on the pharmacokinetic behavior of acetylsalicylic acid (ASA), given 30 min after NOCLO, were studied in two single-blind, parallel-group trials. The trials were performed in 15 male healthy volunteers (age 21-25 years, body weight 62-94 kg, body height 172-187 cm) with known N-acetylation and debrisoquine type hydroxylation phenotype.

Effects of nocloprost on some monooxygenases of rat and human liver.

Interactions of the cytoprotective agent nocloprost (9 beta-chloro-16,16-dimethyl-prostaglandin E2, CAS 79360-43-3) with the microsomal monooxygenase system were studied in rat and human liver. Nocloprost did neither bind to human and rat liver cytochrome P-450 nor changed the activities of aniline hydroxylase, aminopyrine demethylase, ethylmorphine N-demethylase, 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylase as well as 7-pentylresorufin O-depentylase after in vitro incubation with 1 ng/ml. Premedication of rats with 0.

Potential pharmacokinetic interactions of nocloprost clathrate with retarded theophylline and enteric coated diclofenac after single and repeated premedication in healthy volunteers.

Pharmacokinetic interactions of cytoprotective prostaglandin E2 analog nocloprost clathrate with theophylline and diclofenac were studied in two placebo controlled, single-blind studies with parallel groups (n = 8) in healthy male volunteers (age 20-32 years, body weight 63-95 kg, body height 169-193 cm, Broca index 0.81-1.18).

Activation of human blood platelets induced by nocloprost, a stable prostaglandin E2 derivative.

Nocloprost, a 9 beta-chloro-16,16-dimethyl derivative of prostaglandin E2 (PGE2), belongs to the gastric cytoprotective agents that are used in the therapy of gastric ulcer. Since methylated derivatives of PGE2 are known to have proaggregatory effects the influence on platelets was studied. In platelet-rich citrated plasma, nocloprost (> 0.

[Nizatidine in therapy and prevention of non-steroidal anti-rheumatic drug-induced ulcers in rheumatic patients].

269 patients with various rheumatic disorders who had been treated with non-steroidal anti-inflammatory drugs (NSAID) for at least three weeks, were enrolled in this randomised double-blind multicenter trial. Entry criteria were both the presence of an ulcer in gastric and/or duodenal mucosa (> 3 mm and < 20 mm in diameter) as well as dyspeptic symptoms. The patients had been treated with 150 mg nizatidine nocte (n = 86), 2 x 150 mg/d (n = 93) and 2 x 300 mg/d (n = 90) nizatidine.

Effects of nocloprost (9 beta-chloro-16,16-dimethyl PG E2) on absorption and disposition of antipyrine and sulfamethazine in healthy volunteers.

Prostaglandins are known to interfere with drug metabolizing processes. Nocloprost (9 beta-chloro-16,16-dimethyl PG E2) is a promising new cytoprotective prostaglandin in clinical evaluation for the treatment of ulcer disease and prophylaxis of gastric lesions caused by NSAID. Pharmacokinetic interactions of 400 micrograms nocloprost with 15 mg/kg antipyrine and 500 mg sulfamethazine (all given p.

Nocloprost, a unique prostaglandin E2 analog with local gastroprotective and ulcer-healing activity.

Nocloprost (9 beta-chloro-16,16-dimethyl prostaglandin E2 (PGE2)) was examined for gastroprotective and ulcer-healing activity and compared to 16,16-dimethyl PGE2 (dmPGE) in rats. Nocloprost given intragastrically (i.g.

Gastric protection by nocloprost against aspirin damage in humans. Possible role of epidermal growth factor.

Ten healthy young male subjects took part in a double-blind, placebo-controlled crossover study to assess the effects of nocloprost on gastric microbleeding and endoscopic mucosal injury induced by the administration of aspirin (2.5 g). In addition, basal and pentagastrin-induced gastric acid and pepsin secretion and salivary and plasma contents of epidermal growth factor (EGF) were measured after placebo plus aspirin or nocloprost plus aspirin treatment in these subjects.

[Biological testing of biomaterials in the framework of permitted procedures. 2].

Submitted is the revised version of a proposal for a guideline for biological testing of materials (biomaterials) which remain temporarily or permanently, resp., at or in the human body or have contact with drugs or body fluids outside the human body.

[Therapy of endometriosis with dienogest].

Dienogest (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9-dien-3-one, VEB Jenapharm, Jena, GDR), an orally active 19-nortestosterone derivative, was used firstly in the treatment of endometriosis. 57 patients (age 17-45 years) have been entered into the study. The diagnosis was confirmed by laparoscopy or laparotomy in 56 cases and in one case clinically.

[Postcoital contraception with dienogest].

Fifty eight fertile female volunteers between 20 to 45 years were enrolled in a clinical trial to evaluate the efficacy and tolerance of the progestin dienogest (17 alpha-cyanomethyl-17 beta-hydroxyestra-4,9-dien-3-one, VEB Jenapharm Jena GDR) as a postcoital contraceptive. An oral dose of 2 mg dienogest was administered immediately after each coitus. The 58 women reported 872 intercourses during 302 cycles.

[Tissue distribution of iso-metronidazole and metronidazole in tumor-bearing C3H inbred mice].

Among the group of nitroimidazole radiosensitizers, predominantly misonidazole and metronidazole have so far been submitted to an extensive clinical testing. However, neurotoxic side effects have limited the dose of the substance necessary to obtain a maximal effect of sensibilization. Therefore, extensive efforts are being undertaken in the search for new compounds of equally good radiosensitizing action but with less side effects.

[Gas chromatographic analysis in the detection of anaerobes].

By means of gaschromatography a rapid (ca 30 min) diagnosis of anaerobic infections is possible. The principle of a simple technique regarding the equipment and the laboratory-chemical process is presented.

[Pharmacokinetics of metronidazole during perioperative short-term prophylaxis in cesarean section].

Placental transfer and elimination of metronidazole and its main metabolites, 1-(2-hydroxyethyl-)2-hydroxymethyl-5-nitroimidazole (metabolite I) and 2-methyl-5-nitroimidazole-1-acetic acid (metabolite II) were studied in newborn infants and compared with maternal data obtained in 8 high-risk parturients who were subjected to Caesarian section after intravenous infusion of 500 mg metronidazole. Unchanged metronidazole is rapidly transferred across the placental membranes. Its concentrations were the same in maternal venous blood and in both umbilical vessels at delivery.

[Metronidazole in the treatment and prevention of infections in gynecology and obstetrics].

Metronidazole which has been widely used in the treatment of trichomoniasis urogenitalis is the most active agent available against obligate anaerobes.--In this review the present data about antimicrobial activity, mode of action, pharmacokinetic behaviour, dosage, clinical use in gynecology and obstetrics and side effects of metronidazole are outlined.

Disposition kinetics of metronidazole in children.

The pharmacokinetics of metronidazole was studied in 20 paediatric patients aged 6 weeks and 4 to 14 years, who had trichomonal vaginitis or an anaerobic bacterial infection. The dosage of metronidazole was about 10 or 20 mg/kg b.i.

[Distribution of salicylic acid and hydrolysis of acetylsalicylic acid in the human fetus in early pregnancy].

The materno-fetal transfer of salicylic acid and its distribution in the fetal organism was investigated in women of early pregnancy. Acetylsalicylic acid (Acesal) was administered orally in a single dose or in repeated doses at different times before legal interruption. The mean passage rates were about 6-15%.

[Metronidazole for treatment of puerperal mastitis (author's transl)].

Pathogenic anaerobic bacteria may be among the causes of puerperal mastitis which, therefore, was treated by the authors with metronidazole (Vagimid) and with antibiotics, such as penicillin, oxacillin, erythromycin, and oxytetracycline. Best results were obtained by administration of metronidazole to patients in early mastitis. The frequency of incisions was reduced.

Enzymatic activity in carbohydrate metabolism in human liver during development.

The age dependence of the enzymatic activities hexokinase, glucose-6-phosphate dehydrogenase, and glutathione reductase in the fetal human liver was estimated and the activities were compared with the same enzymatic activities in adult human liver.