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M Doersing

Publications and source records attributed to M Doersing.

6 recordsLinked to original sources
PubMed1992

[Plasma- and tissue concentrations following intramuscular administration of etofenamat. Pharmacokinetics of etofenamat and flufenamic acid in plasma, synovium, and tissues of patients with chronic polyarthritis after administration of an oily solution of etofenamat].

Studies on Plasma and Tissue Concentrations of Etofenamate following Intramuscular Application/Pharmacokinetics of etofenamate and flutenamic acid in plasma, synovia and tissues of patients with chronic polyarthritis after application of oily etofenamat solution Pharmacokinetics of etofenamate (ETO, CAS 30544-47-9; Rheumon i.m.) and flufenamic acid (FLU, CAS 530-78-9) were investigated in plasma, synovial fluid, and tissues after single intramuscular application of etofenamate to patients with rheumatoid arthritis. 62 patients with indicated operative procedure in the knee-joint received a single dose of etofenamate dissolved in oil before operation. At definite times between 1.5 and 48 h post injectionem samples from 6 patients of each time group were collected. Samples of plasma, synovial fluid, synovial membrane, muscle, bone, hyaline cartilage, and fat tissue and in some cases meniscus cartilage were taken. Concentrations of ETO and its active metabolite, FLU, were determined by HPTLC. In all tissues investigated, concentration/time courses of ETO and FLU were observed. ETO and FLU were measured first in all matrices 1.5 h at the latest 3 h post injectionem. Pharmacokinetics in tissues follows that in plasma. Rate-limiting step is the liberation of drug from the oil depot. For a long period pharmacokinetics of ETO and FLU is mainly determined by the constant liberation from the oil depot (zero order kinetics of liberation). Zero order kinetics is deduced from the linear ascent of the cumulated AUC (in percent) vs. time plot. It is directly related to the liberation of drug from the galenical formulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

[Retard effect of acemetacin from a commercial preparation--kinetics in humans following single and multiple administration].

Acemetacin was given to 14 volunteers in a randomized cross-over arrangement as one single administration of 90 mg (1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxyacetic acid) (as Rantudil, Rantudil forte and Rantudil retard) and the courses of blood levels curves compared. Half-life of absorption was considerably higher with the retard formulation (2.01 instead of 0.58 h). The blood level maximum (tmax) was significantly (p less than 0.05) delayed by the retardation, blood levels were lower after 2 h (p less than 0.01), not significantly different 3-4 h after administration and higher (p less than 0.05) than the immediate release form after 6-10 h. AUC's are 5.82 +/- 4.04 (normal) and 6.75 +/- 3.24 (mumol X l-1 X h retarded). The mean residence time was prolonged from 4.1 to 6.3 h, yielding a sustained release quotient of 1.54. After multiple administration (2 retard capsules/d for 8 d) cmax corresponded to the results obtained after single application, maximum levels at 1.24 mumol X l-1 (mean) being somewhat higher than after single application (1.11 mumol X l-1), which is the usual steady-state behavior. Minimum levels in the steady-state (cmin) were 0.24-0.53 mumol X l-1. Bioavailability (AUC's between applications) was not significantly different. No accumulation was found. Levels measured during 8 days of administration of the Rantudil retard formulation corresponded to blood levels from computer simulations. Biological half-life was 4.03 h, which was similar to data obtained with Rantudil (3 X 60 mg/d) in rheumatic patients.

Delayed-Action Preparations↗
PubMed1981

[Metabolism of etofenamate / Identification and analytic of metabolites, their pharmacological properties and species dependence of metabolism (author's transl)].

After oral application of etofenamate to animals (rat, rabbit, dog, monkey) unchanged etofenamate and numerous metabolites are found in urine. Analytical properties (thin-layer chromatographic behavior, UV- and fluorescence data) of etofenamate, 5-hydroxy-, 4'-hydroxy, 5,4'-dihydroxy-etofenamate, flufenamic acid, 5-hydroxy-, 4'-hydroxy-, 5,4'-dihydroxy-flufenamic acid are described. Derivatives of etofenamate and flufenamic acid are excreted by rabbit, dog, monkey and man, whereas flufenamic acid derivatives are excreted preferentially by rats; profound degradation takes place in dogs. Metabolism in man is more similar to monkey than to dog and rodents. Metabolic pattern after oral and cutaneous application is quite similar. The six hydroxy derivatives have no pharmacological activity--they do not contribute to the pharmacological action of the substance.

Animals↗
PubMed1980

[Analytical methods and in vitro studies with acemetacin].

1. Analytical methods (isolation, TLC, UV-spectroscopic and preferably fluorimetric determination) of [1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy] acetic acid (acemetacin, TV 1322, Rantudil), its analogues, hydrolysis-products and metabolites from biological material are described. 2. Stability is also dealt with. Hydrolysis of the p-chlorobenzoyl group results in strongly fluorescing compounds and can be used in determination of acemetacin, indometacin and derivatives 3. Proof is given that in in vitro studies, such as e.g. Mizushima's protein turbidity test or the test for inhibition of prostaglandin-synthetase, only intact acemetacin (and none of its potential break-down products) is present and is active. 4. In in vitro studies, such as the inhibition of total complement and of the increase in activity of serum sulfhydryl groups, acemetacin and a series of its salts proved to be at least as effective as indometacin. 5. In comparing protein binding, acemetacin, like indometacin, is found to bind strongly to albumin. The portion of free, non-protein bound acemetacin, which thus remains available for the pharmacological action, is found to be approx. 60% higher than the corresponding portion of free indometacin.

Animals↗
PubMed1980

[Metabolism and pharmacokinetics of acemetacin in man (author's transl)].

Metabolism and pharmacokinetics of [1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy]-acetic acid (acemetacin, TV 1322, Rantudil) in comparison to equimolar doses of indometacin was investigated in human volunteers after a single oral application and in rheumatic patients after multiple application. After multiple application (t.i.d. for 10 days) of equimolar doses of acemetacin and indometacin, mean blood level curves. The bioavailability of acemetacin derived from these data, corresponds to that of indometacin, i.e., approx. 100%, whereas after a single dose bioavailability of acemetcin is found to be smaller (66% from blood level, 64% from urine). This difference between single and multiple application is explained by slow filling-up of compartments. Degradation of acemetacin occurs by esterolytic cleavage to indometacin, by O-demethylation and N-desacylation and by partial conjugation of all these compounds to glucuronic acid. Blood level ratios of acemetacin and indometacin are equal after single and after multiple application of acemetacin. Therefore, degradation of acemetacin is not induced after multiple application. After a steady-state has been reached half-life of elimination is 4.5 +/- 2.8 h, which is longer than for indometacin (2.2 +/- 0.5 h). Interindividual differences are in the same range as described for indometacin.

Anti-Inflammatory Agents↗