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J Schnitker

Publications and source records attributed to J Schnitker.

53 records · Page 3Linked to original sources
PubMed1982

[Investigations to gastric tolerance of a sustained release theophylline formulation (author's transl)].

The measurement of the transmural gastric potential difference (PD) is a suitable method to quantify irritations of the human gastric mucosa caused by drugs. Purpose of this investigation was to check the gastric tolerance of Bronchoretard, a new developed "divided-dose" drug formulation of theophylline as retarded pellets in capsules in comparison to pure theophylline solution. After having checked the suitability of the procedure in respect of the obtained results, a study on 7 healthy male volunteers was considered to be justifiable, as the development of retarded theophylline preparations, which cause lower irritations in the stomach by slower release of pure theophylline, has a high therapeutic value. With the gastric PD model, developed at our institute following variables were calculated: the area under the baseline (AUB), the "Reizindex" (RI), the mean instability time (MIT) of the membrane and the maximum potential difference (Pdmax). The volunteers wee admitted to the ward of our institute 36 h before the first application. On 2 different days 350 mg theophylline, dissolved in 50 ml physiological saline as well as 1 capsule Bronchoretard containing 350 mg theophylline, were administered Cross over according to a randomisation plan and the deviation of the PD was measured as a function of time. The study led to the following results: after administration of Bronchoretard the AUB is statistically significant smaller than after administration of theophylline solution (P less than 0.05). After administration of Bronchoretard the RI is statistically significant smaller than after administration of theophylline solution (p less than 0.05). After administration of Bronchoretard the mean instability time is statistically significant smaller than after administration of theophylline solution (p less than 0.05). After administration of Bronchoretard Pdmax is smaller in trend than theophylline solution (p greater than 0.05). The oral administration of Bronchoretard leads to considerably lower irritation than the instillation of the same dose of theophylline in solution.

Adult↗
PubMed1979

[Prevention of urinary tract toxicity of oxazaphosphorines by a "uroprotector". Report on a field study (author's transl)].

In an open multicenter phase III trial, prophylaxis of the urinary tract with sodium 2-mercaptoethanesulfonate (Mesnum) was carried out in 242 patients treated with oxazaphosphorines for various malignant tumors. Under the protection of Mesnum 29 patients were treated with cyclophosphamide (Endoxan), 195 with ifosfamide (Holoxan) and 8 with trofosfamide (Ixoten). Other cytostatics were also used (polychemotherapy) in 92 cases. On administration of Mesnum, 7 macrohematurias reappeared, only 3 of them however with correct application, and 22 microhematurias, 12 of them with correct application. Cylindrurias were re-established in 3 patients. In Mesnum we have a compound which can control the urotoxicity ("uroprotector") of oxazaphosphorines which limits their therapeutic use.

Adolescent↗
PubMed1979

Controlled clinical studies with an antidote against the urotoxicity of oxazaphosphorines: preliminary results.

A randomized study in 20 patients with cancer was carried out to test the clinical efficacy of sodium-2-mercaptoethane sulfonate (ASTA D-7093; mesnum) as an agent to prevent urotoxic side effects (in particular, hemorrhagic cystitis) during cytostatic therapy with the oxazaphosphorines cyclophosphamide and ifosfamide. Eleven patients received mesnum iv and nine patients received a standard prophylaxis. The frequency of microhematuria was significantly lower in the patients receiving mesnum. A slight microhematuria was observed in one patient. With the standard prophylaxis, all nine patients receiving single-agent therapy with ifosfamide or cyclophosphamide had hematuria and three of these had macrohematuria. According to the available results, a daily mesnum dose of 60% (wt/wt) of the ifosfamide or cyclophosphamide dose is recommended. This dose should be divided into three equal fractions. The first administration should be given concurrently with the cytostatic agent and the subsequent two administrations at 4 and 8 hours after administration of the cytostatic agent. Significantly higher doses of mesnum (eg, 133% of the cyclophosphamide or ifosfamide doses) lead to gastrointestinal disorders, which are easily reversible.

Clinical Trials as Topic↗
PubMed1979

[Comparative examination of theophylline-serum-concentrations and bronchospasmolytic effect of cholintheophyllinate (euspirax) and theophyllin-aethylendiamine (euphyllin retard) in patients with obstructive airway diseases (author's transl)].

12 patients with obstructive airway diseases were given a single oral dose of 400 mg resp. 600 mg Cholintheophyllinate (Euspirax) and 350 mg Theophyllin-Aethylendiamine (Euphyllin retard). In an intra-individual comparative study the theophylline-serum-concentrations and the bronchospasmolytic effects of both drugs have been checked over a period of 12 hours. A very good resorption and the highest mean blood levels of 9,13 +/- 2,88 mg/1 resp. 12,11 +/- 2,55 mg/1 resulted from Cholintheophyllinate 2 hours after application. The effect on the lung function parameters was most expressed 2 to 4 hours after application of this drug and correlated well with the theophylline-blood-levels. The higher dose of Euspirax was followed more frequently by side effects. 2, 4 and 12 hours after application of Euphyllin retard the serum-concentrations were strikingly low. The mean values were 2,04 +/- 1,22 mg/l, 3,00 +/- 2,18 mg/l resp. 3,38 +/- 2,01 mg/l. In spite of the low blood levels a significant improvement of the lung function parameters could be noticed after 4 to 6 hours. The qualities of both drugs as to their bioavailability and effect on airway obstruction shall be examined by means of another comparative study.

Adult↗
PubMed1979

[Pharmacological study on treptilamine in man/study on tolerability (author's transl)].

N,N-Diethyl-N-(2-[alpha(tricyclo[2,2,1,0(2,6]hept-3-ylidene)-benzyloxy]-ethyl)amine hydrochloride (treptilamine) which in experiments on animals showed distinct spasmolytic effects, has been investigated first in 6 volunteers with regard to compatibility using different doses p.o. and i.v. In connection with this previous study a double blind study including placebo was performed for verification of the observed effects. In the plot study 30, 40 and 50 mg were applied orally and 10, 15 and 20 mg treptilamine were used i.v. The double blind study was designed for 20 volunteers at dosages of 40 mg p.o. and 15 mg i.v. against placebo. In the pilot study systolic blood pressure decreased significantly 5 to 15 min after i.v. application of the substance for 5 or 30 min. The range of accommodation was restricted depending on the dose used. No alteration of circulation was observed after oral application at any dose. All volunteers felt tired. A significant decrease of systolic blood pressure (15 mmHg for 10 min immediately after application) occurred after 15 mg of substance were applied i.v. in the double blind study. No effect on circulation could be seen after placebo. The range of accommodation was restricted in a significant way both after i.v. application (40%) and after oral application (30%). Two of five volunteers recorded a burning sensation in the venous wall which was followed by drowsiness. One volunteer felt increasingly tired after oral application. No influence of the substance could be seen on the clinicochemical parameters examined.

Accommodation, Ocular↗
PubMed1976

Evaluation of a cooperative clinical study of the cytostatic agent ifosfamide.

In cooperative studies performed in 21 German clinics, the new cytostatic agent 3-(2-chloroethyl)-2-[(2-chloroethyl)-amino]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide (ifosfamide; trade name: Holoxan) was administered as massive-dose treatment. The studies aimed at confirming the results obtained in pharmacological and Phase I clinical trials with a fractionated administration of ifosfamide on a large scale. The study was carried out in 390 patients suffering from various malignant conditions. The majority of patients had had pretreatment without response or were admitted at an advanced stage of disease. Despite this negative selection, 25.5% of the patients showed an initial full remission and 42.3% partial remission; in 32.2% of the patients, reduction of the tumour signs by at least 50% was not attained. After an average observation period of 6 1/2 months, 53.8% of the patients were still alive. The study clearly shows the superiority of fractionated administration of ifosfamide when compared to its use as a single administration. In addition, the rates of remission and survival, and of survival times, were clearly dependent on dosage, independent of the tumour type. A daily dosage of 50 to 60 mg/kg ifosfamide on 5 consecutive days produced the best results. In spite of the fact that ifosfamide was not always given at optimum dosage, it proved to be definitely superior to conventional chemotherapy in testicular tumours, particularly teratomas and also in hypernephromas. Retrospective comparison with results of conventional chemotherapy for ovarian, bronchial and mammary cancer has shown ifosfamide to produce the same therapeutic effect in these tumour types. In this study group, leukopenia was not regarded as a limiting factor to the administration of ifosfamide. Side effects in the efferent urinary tract, particularly cystitis, were controlled with adequate preventive measures.

Adenocarcinoma↗
PubMedDate not supplied

Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs.

OBJECTIVE: The objective of this study was to establish the non-inferiority of an oral enzyme therapy (Phlogenzym-(PE)) as compared to the non-steroidal anti-inflammatory drug (NSAID) diclofenac (DC) in patients with osteoarthritis (OA) of the hip. METHODS: Ninety patients presenting with painful episodes of OA of the hip were treated for 6 weeks in one study centre in a phase III, randomised, double blind, parallel group trial. Altogether, 45 patients were treated in the PE group and 45 patients were treated in the DC group. Primary efficacy criteria were: WOMAC dimensions pain, joint stiffness and function, and Lequesne index as multiple endpoint according to O'Brien. The efficacy criteria were analysed applying the test of non-inferiority with regard to mean changes and frequencies, t-test, U test, ANCOVA and descriptive methods. RESULTS: Within the 6 weeks observation period, the adjusted changes from baseline to endpoint of the target parameters worked out as follows (adjusted differences, mean +/- SEM): WOMAC subscale pain (PE -10.3 +/- 1.2, DC -9.5 +/- 1.2), WOMAC subscale joint stiffness (PE -3.9 +/- 0.5, DC -3.6 +/- 0.5), WOMAC subscale physical function (PE -31.7 +/- 3.5, DC -29.7 +/- 3.5), Lequesne's index (PE -2.89 +/- 0.47, DC -2.27 +/- 0.47). Non-inferiority of PE as compared to DC with regard to the O'Brien's global sum of the standardised adjusted changes from baseline to endpoint in pain, stiffness, physical function, and Lequesne's index was established with p = 0.0025. PE was simultaneously non-inferior as compared to DC with regard to the 4 single endpoints: WOMAC subscale pain (p = 0.0033), WOMAC subscale joint stiffness (p = 0.0061), WOMAC subscale physical function (p = 0.0039), Lequesne's index (p = 0.0008) (closed test procedure). The equivalence tests remained insignificant due to comparatively lower effects of DC. For 71.1% of the PE patients and for 61.4% of the DC patients rates of good or very good global investigator assessments of efficacy were calculated (test of non-inferiority: p = 0.0011). In the majority of patients, tolerability was judged in both drug groups as very good or good. CONCLUSION: This trial showed significant non-inferiority from 6 weeks treatment with PE in patients with OA of the hip with regard to the WOMAC dimensions pain, stiffness and physical function, to Lequesne's index, to the investigator and patients assessments of efficacy, and to the responder rates based on pain, physical function, and patient assessment of efficacy. With regard to drug tolerability some tendencies in favour of PE were detected. However, in this study there was no real difference between PE and DC 100 mg/day, implying an equal benefit-risk relation between the substances. PE may well be recommended for the treatment of patients with osteoarthritis of the hip with signs of inflammation as indicated by a high pain level.

Activities of Daily Living↗
PubMedDate not supplied

Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: a randomised, placebo-controlled, double-blind, multicentre clinical trial.

The objective of this randomised, multicentre, double-blind clinical trial was to investigate the impact of PS76A2, an aqueous mistletoe extract standardised to mistletoe lectins, on quality of life (QoL) in breast cancer patients. A total of 352 patients were randomly allocated to 2 groups receiving PS76A2 (15 ng mistletoe lectin/0.5 ml) or matching placebo twice weekly for 4 to 6 cycles of CMF (cyclophosphamide, methotrexate, fluorouracil) chemotherapy followed by 2 months follow-up. The primary efficacy end-point was the change from baseline of 3 FACT-G subscales (physical, emotional and functional well-being) during the fourth CMF cycle. Secondary measures included GLQ-8 (8 linear analogue self-assessment scales), Spitzer's uniscale and haematological variables. The main variables of safety analysis were adverse events, including injection site reactions and clinical laboratory tests. The results showed that physical, emotional and functional well-being improved upon PS76A2, but deteriorated following placebo. The treatment differences were statistically significant for the 3 subscales as well as for the summary score FACT-G, which was analysed as O'Brien's rank sum of its 3 subscales: The total score increased by 4.40 +/- 11.28, indicating a higher QoL after PS76A2, but decreased by 5.11 +/- 11.77 with placebo (p<0.0001). The GLQ-8 sum of 8 LASA scales was analysed as a summary score of GLQ-5 (sum of item nos. 1, 5, 6, 7, 8) and GLQ-3 (sum of item nos. 2, 3, 4). GLQ-5 characterises typical aspects of QoL, while GLQ-3 consists of 3 side-effects of CMF (feeling sick, numbness or pins and needles, loss of hair). GLQ-5 decreased by 42.9 +/- 125.0 upon PS76A2, indicating an improvement in QoL, but increased by 60.3 +/- 94.0 upon placebo (p<0.0001). GLQ-3 deteriorated in both groups (PS76A2: 13.9 +/- 52.4; placebo: 34.5 +/- 57.0), but the differences in favour of PS76A2 were, nevertheless, statistically significant (p=0.0007). The total score GLQ-8 improved by 28.9 +/- 154.6 after PS76A2 and deteriorated by 94.8 +/- 141.1 after placebo (p<0.0001). Spitzer's uniscale improved by 12.2 +/- 30.7 upon PS76A2 and deteriorated by 10.8 +/- 26.1 with placebo (p<0.0001). After follow-up without chemotherapy, a significant treatment difference in favour of PS76A2 was determined by means of FACT-G, GLQ-8 and Spitzer's uniscale. PS76A2 was well tolerated in this trial, with the exception of slight local reactions in 17.6% of the PS76A2 group. In conclusion, PS76A2 (15 ng mistletoe lectin/0.5 ml twice weekly) was shown to be safe and effective in improving QoL in breast cancer patients during chemotherapy and follow-up.

Adult↗