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Biomedical subjects

W Rupp

Publications and source records attributed to W Rupp.

At least 37 records · Page 2Linked to original sources
PubMed1981

[Adequate and inadequate trials in "clinical" pharmacology].

Our definition, based on 14 years of practical experience, is as follows: In clinical pharmacology, a procedure is adequate if it can be used in normal subjects in a non-invasive way and if it generates relevant information concerning pharmacotherapy in patients. Six examples are discussed in detail; the variable body weight may cause wide variations, for example, in absorption characteristics; unhomogeneous groups of subjects are likely to lead to poorly reproducible results. Body position and food intake (individual eating habits) may disguise drug effects by creating additional "noise". By titrating the heart rate during work load on the ergometer in order to achieve and maintain a target rate, individual differences in physical fitness and skill can be eliminated. Orthostatic regulation of cardiovascular variables may be impaired without concomitant psychic lability. The latter indicates predisposition to placebo responses, e.g. in studies using the standardized tourniquet pain model and mild analgesics. In normal subjects computer analysis of cerebral biosignals in combination with psychometric and behavioural tests usually gives more reliable information as compared to the patient pretreated with different drugs.

Body Weight↗
PubMed1980

Some aspects of the clinical pharmacology of furosemide.

Earlier data on kinetics and dynamics of furosemide given to normal humans are reviewed and the role of different assay methods for the calculation of kinetic variables is emphasized. Adequate timing of serum samples may help to solve the "tail problem", i.e. the increasing loss of precision in the vicinity of the limit of detection. New aspects are reported from studies with a pellet-dosage form of furosemide. Initial peak diuresis is reduced and the duration of action is prolonged. Clinical results in hypertensive patients are in agreement with the data achieved in normal subjects.

Diuresis↗
PubMed1979

Standardized mental stress in healthy volunteers induced by delayed auditory feedback (DAF).

Using delayed auditory feedback (delay 0.175 s) a standardized form of mental stress was investigated in 8 healthy male volunteers. After a resting period and a period of undelayed reading, the volunteers were exposed for 5 min to the DAF stress. During the DAF period heart rate increased by 10% and systolic and diastolic blood pressure increased by 9% and 18%, respectively. As a measure of acute sympathetic activation, plasma concentrations of norepinephrine and epinephrine rose by 68% and 49%, respectively. The activity od dopamine-beta-hydroxylase in plasma was increased by 25%. From these results it can be concluded that the DAF procedure provides a suitable method for inducing a standardized mental stress in normal subjects, which can be measured as changes in biochemical and cardiovascular variables.

Acoustic Stimulation↗
PubMed1979

Pharmacokinetics of single and multiple doses of clobazam in humans.

1. The pharmacokinetics of clobazam and its biotransformation product N-desmethylclobazam were investigated after single and multiple doses in normal subjects. 2. The relevant physicochemical properties of clobazam were measured and are presented. Different assay methods (radiochemical, fluorimetric and gas chromatographic) were applied and the results correlated. 3. After single doses the pharmacokinetic profile of clobazam includes time to peak levels 1--4 h after dosing, peak levels increasing linearly with the logarithm of dose, and terminal half-lives of about 18 hours. At least 87% of an oral dose is absorbed, as indicated by urinary recovery of labelled material. 4. In multiple-dose studies unchanged clobazam levelled off at minimum steady-state concentrations within one week of dosing. During 28 d of medication N-desmethylclobazam accumulated to near steady-state levels about eight times higher than those of the unchanged compound. 5. No pharmacokinetic interactions were discovered between clobazam and the antidepressant nomifensine.

Anti-Anxiety Agents↗
PubMed1979

Pharmacodynamic comparison of the acute effects of nomifensine, amphetamine and placebo in healthy volunteers.

In a double blind cross over trial the effects of single doses of 100 mg nomifensine, 15 mg racemic amphetamine and placebo were compared in 9 healthy volunteers. Assessments of choice reaction behavior, simple reaction time, critical flicker fusion and attention on continuous calculations were performed together with a series of self rating scales, a side-effect list and vital signs before and 90 min., 180 min. and 360 min. after each administration. While the only significant nomifensine effect was an increase of correct solutions in the continuous calculation task, amphetamine differed from nomifensine and placebor in a number of subjective variables which describe emotional changes typical for drug stimulation. Subjects also expressed the will to have amphetamine prescribed for fatigue and loss of drive, whereas preferences for nomifensine were virtually the same as for placebo. Under amphetamine heart rate and blood pressure were increased and side-effects were frequent. It is concluded that nomifensine showed none of those subjectively pleasant amphetamine effects which are responsible for the reinforcement function leading to amphetamine dependence.

Adult↗
PubMed1977

[The liver and the so-called absorption deficit. Results of animal experiments (author's transl)].

Experiments with ethanol were performed in two dogs with indwelling catheters in the portal vein, in the hepatic vein and the aorta. 2.5, 2.0 and 1.5 g ethanol per kg bodyweight in 10% aqueous solution were administered via stomach tube. A loss of ethanol during the first pass through the liver could be measured both in experiments after 24 hours fasting and after feeding. However, these findings do not completely explain the problem of the socalled "Resorptionsdefizit" of ethanol. It is concluded that the absorption of ethanol from the gastrointestinal tract is mainly influenced by factors related to foodintake.

Animals↗
PubMed1977

Determination of nomifensine by a sensitive radioimmunoassay.

1. A radioimmunoassay (RIA) has been developed for determination of both nomifensine and total nomifensine (nomifensine + conjugated nomifensine) in serum, plasma, and urine. 2. Antibodies were prepared in rabbits by immunization with N-(8-Nomifensine) succinamic acid-bovine serum albumin. 3H-labelled drug was used as tracer. Separation of free from antibody-bound nomifensine was carried out using dextran-coated charcoal. For determination of total nomifensine, the acid-labile conjugate was split by acidification. 3. The limit of detection for nomifensine is 300 pg/ml plasma and the cross-reactivity of the metabolites is less that 1%. The influence of conjugated nomifensine on the results of nomifensine can be corrected. 4. Pharmacokinetics of nomifensine were determined in healthy volunteers after oral administration of 100 mg 14C-labelled drug. Peak levels of 14C radioactivity (2,150 ng/ml), total nomifensine (1,252 ng/ml) and nomifensine (53 ng/ml) appeared within 1.5-2 h; the half-life of elimination from plasma was 1.5-2 hours. The advantages of this routine method are high sensitivity, the requirement of small amounts of plasma, and simple handling.

Administration, Oral↗
PubMed1977

Kinetic interaction of nomifensine with a 1, 5-benzodiazepine (clobazam).

1. Among the numerous possibilities of drug interactions, pharmacokinetic interactions may cause mutual changes in absorption, distribution, metabolism and elimination of either drug. In the present study this approach was used to investigate pertinent effects of nomifensine and clobazam. 2. Ten normal subjects participated in an intra-individual comparison of nomifensin 75 mg alone and in combination with clobazam 15 and 30 mg. The study design was carried out according to a Latin square in double-blind conditions. One-week wash-out periods were used between the trial days. Serum levels of nomifensine were measured by radioimmunoassay (RIA) and of original clobazam by gas chromatography (GC). Classical criteria for bioavailability (peak serum levels, time of peak, area under the serum level time curve) and the half-life of elimination from the serum were used for retrieval of pharmacokinetic information. 3. Results showed no relevant differences in the criteria mentioned above, after administration of each drug alone or in combination. Therefore, extrapolations were made to multiple dose kinetics based on assumptions derived from practical therapy. They showed comprehensive agreement with therapeutic results in depressed patients. 4. The use of the classical criteria for bioavailability, in addition to the calculation of the half-time of elimination from serum, provides sufficient information for the decision whether pharmacokinetic drug interaction is present or absent. There was no such interaction after single doses of nomifensine or clobazam.

Adult↗
PubMed1977

[Finding the effective dose of diuretics in man (author's transl)].

After a short survey of the classes of diuretics the procedures are described which are available to find effective doses of newly synthetized compounds in animal experiments. The method of Lipschitz and its modifications used for screening in rats are discussed in more detail. From the practical view of the clinical pharmacologist an explanation is given of the problems encountered in planning a study, balancing fluid- and electrolyte intake and in the suggestions for dose extrapolations to man. The experimental development in animals and healthy humans is demonstrated by means of the new diuretic compound Hoe 747. A synoptic graph showing the estimated dose-response curves emphazises the fact that it is possible to extrapolate the first dose in man from animal data with sufficient precision.

Animals↗
PubMed1976

Furosemide and bumetanide: a study of responses in normal English and German subjects.

Diuretic responses to oral administration of 1 mg bumetanide and 40 mg furosemide were determined in double-blind, crossover balanced trials in 10 normal English subjects and 6 normal German subjects. In each experiment the 0- to 8-hr urine volume and sodium excretion were significantly higher after bumetanide, potassium excretion did not differ, and the Na/K ratio, although higher after bumetanide, was not significantly different by analysis of variance. In German subjects the diuretic and natriuretic responses to both drugs were greater and the potassium excretion less than in English subjects. In the English, the pretreatment 24-hr urinary Na/K ratio correlated with the urinary Na/K ratio response to both drugs and with the potassium excretion after furosemide. The mean plasma uric acid before treatment correlated with the Na/K ratio and potassium excretion after furosemide. Aldosterone excretion did not correlate with response to either diuretic. The mean pretreatment 24-hr log10 Na/K ratio in the two treatment periods of the English and German subjects correlated with the mean sodium excretion, potassium excretion, and log10 Na/K after the two diuretics, thus providing a partial explanation for intersubject and interstudy variation. Pretreatment log10 Na/K could also explain intrasubject variation, justifying its use as a covariate in covariance analysis. This demonstrated that at this dose ratio the urinary log10 Na/K ratio response to bumetanide was significantly higher than that to furosemide.

Aldosterone↗
PubMed1976

[Studies on the pharmacodynamics and compatibility of the local anesthetic carticain].

Two local anesthetics were compared with a placebo with regard to subjective tolerance and influence on driving capacity in a double blind test in eight male probands. Neither performance, the ability to respond, reactivity, nor fine motor coordination were reduced or impaired five to sixty minutes after a submucous injection of 3.6 ml of the local anesthetics tested. There were no changes of self-evaluation in the sense of a changed active-passive polarity.

Anesthesia, Dental↗
PubMed1975

[Studies on the bio-availability of tolbutamide (author's transl)].

Two different batches of Rastinon 1,0 Hoechst were administered, a year apart, to two groups of healthy subjects (ten and six men, respectively) without any difference in effect on blood sugar being found. The blood sugar concentration was measured in six healthy men before and after oral administration of 1,000 mg tolbutamide (as Rastinon 1,0 Hoechst or tolbutamid tablets Ratiopharm), in a blind test. After tolbutamide Ratiopharm, the area under the blood sugar concentration-time curves was only 29 percent (0-4 hafter medication) and 32 percent (4-8 h after medication) of that after Rastinon 1,0 (P 2alpha less than 0.01), with marked scatter between individuals. Maximal serum concentration was 80 percent below that after Rastinon. The first measurable value was reached 0.8 plus or minus 0.2 h after medication of Rastinon and 3.6 plus or minus 0.8 h after tolbutamide Ratiopharm. The areas under the serum concentration under the curves after tolbutamide Ratiopharm were only 16 percent (0-4 h after medication) and 19 percent (0-8 h after medication) of those after Rastinon (P 2alpha less than 0.05 and 0.01, respectively). The differences demonstrate that tolbutamide Ratiopharm tablets and Rastinon 1,0 Hoechst are not equivalent biologically and therapeutically.

Administration, Oral↗
PubMed1975

[Practical evaluation of methods in pharmacokinetics].

A short discussion of the differences between kinetic processes of zero and first order is followed by an outline of evaluation methods used in pharmacokinetic practice, e.g. "paper and pencil methods" as well as the use of digital and analog computers. The increasing potency of new drugs requires not only more sophisticated methods of analysis and expensive facilities but also more complex models to generate pharmacokinetic information.

Computers↗
PubMed1975

[Carcinosarcoma of the larynx (author's transl)].

Case report of a 53-year-old male patient with a carcinosarcoma of the vocal cord. The diagnostic problems of these rare tumors are discussed with a review of the available literature.

Carcinoma, Squamous Cell↗