In a pharmacokinetic study on 18 healthy male volunteers the bioavailability and elimination kinetics of furosemide-retard and the combination furosemide-retard/triamterene were investigated and compared with the non-retarded form and another retard form of furosemide. The relative bioavailability of the non-retarded form of furosemide was distinctly reduced by the retardation in the substances investigated. It varied between 42-66% in the plasma and between 37-73% in the urine. In the combination with triamterene the serum concentration time curve of furosemide was only slightly modified but the renal excretion of furosemide was more influenced (36% for furosemide-retard and 25% for furosemide-retard/triamterene). In comparison, the values for the renal excretion of triamterene and OH-TA sulfate were distinctly greater than those obtained after administration of triamterene alone. A renewed increase of the plasma concentration and renal excretion of furosemide were observed between 9 and 10.5 h after administration of furosemide-retard/triamterene. This observation suggests that a further absorption of furosemide occurs as a consequence of the delayed release from distal parts of the small intestine or from the large intestine.

Absorption↗

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Pharmacodynamics and pharmacokinetics of furosemide-retard and furosemide-retard/triamterene.

In a randomized cross-over study the saluretic effect of furosemide-retard was compared with the combination of furosemide-retard/triamterene in 10 healthy male volunteers. The combination led to a significantly stronger excretion of sodium and a significantly lower excretion of potassium than furosemide-retard. The interaction of the saluretic with the antikaliuretic was even more distinctly expressed regarding sodium related quotients. The combination furosemide-retard/triamterene differs significantly from furosemide-retard in the main considering Na+/Cl-, Na+/K+ and Na+/Mg2+ quotients. The concentration time curves for furosemide and OH-TA-sulphate in the plasma are nearly similar. Maximal plasma levels for furosemide are reached after 3.9h and for OH-TA-sulphate after 2.2h. The 'apparent' elimination half-life time for furosemide is 2.1h and the elimination half-life time for OH-TA-sulphate is 2.0h.

Adult↗

PubMedDate not supplied

Prophylaxis of postoperative thromboembolism by low dose heparin and by acetylsalicylic acid given simultaneously. A double blind study.

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Adult↗

PubMedDate not supplied

The diuretic effect of muzolimine (Bay g 2821) on hepatogenic ascites.

A double-blind study was carried out in 22 patients with hepatogenic ascites to examine the effectiveness of the combination of muzolimine and spironolactone in comparison with combinations of furosemide and spironolactone and placebo and spironolactone. Despite the heterogeneous and variable case material, there was no significant difference between the 3 patient groups prior to treatment. After a diuretic-free preliminary period, all patients received 300 mg spironolactone daily plus 80 mg muzolimine, 80 mg furosemide or placebo for 7 days. Before the start of treatment and at daily intervals, measurements were made of waist size, body weight, and urinary and electrolyte elimination. Blood chemistry was investigated before treatment and on Days 4 and 7. Analysis of the results showed that the combination of muzolimine and spironolactone produced a statistiscally significant stronger saluretic effects than the other two combinations. This can be explained by the different sites of action of muzolimine and spironolactone, resulting in an additive effect. Neither subjective nor objective side-effects were observed during the 7-day treatment period.

Aged↗

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[Distribution of 4-14C-mofebutazone in the rat].

To further elucidate the distribution and differentiation of mofebutazone in comparison to phenylbutazone, 6 rats received 200 mg/kg 4-14C-mofebutazone corresponding to approx. 27 microCi/animal. 2 animals were sacrificed each time after 45 min, 6 h and 24 h. The 4-14C-plasma level was determined at the corresponding test periods and the radioactivity eliminated within 24 h in the urine was also determined. In addition autoradiograms of the whole animal were prepared for each animal. According to this study 4-14C-mofebutazone is distributed mainly in the metabolisation and elimination organs, a moderate activity was to be found under the skin and muscle tissue, but none, however, in the central nervous system and the bone marrow. Nearly 81% of the substance was eliminated after 24 h and with exception the colon the corresponding autoradiograms were practically free of activity. Because of the short half-life time and the rapid elimination mofebutazone does not lead to any accumulation.

Animals↗

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[Pharmacology, toxicology and pharmacokinetics of mofebutazone].

The difference between mofebutazone and phenylbutazone is shown by means of toxicological, pharmacological and pharmacokinetic studies as well as by the protein binding. In spite of a certain chemical similarity both substances differ distinctly. Mofebutazone is approx. 5-6 times less toxic than phenylbutazone but its analgesic and antiphlogistic effects are weaker than those of phenylbutazone. The half life time of mofebutazone of 1.9 h is considerably shorter than that of phenylbutazone (54-99 h). Mofebutazone, in contrast to phenylbutazone, is mainly glucuronidised and to 94% eliminated within 24 h, phenylbutazone on the other hand to only 88% within 21 days. In spite of a high plasma protein binding quota of 99%, mofebutazone is classed among those substances with a medium binding potential. Conclusions may only be drawn with great reservation with regard to a category of substances from the effect and side effects of one substance on the basis of the present studies.

Adult↗

PubMedDate not supplied

[Kinetics of mofebutazone in plasma and synovial fluid].

The kinetics of mofebutazone in the plasma and in the synovial fluid was investigated in a pharmacokinetic study. To this purpose 7 volunteers and 36 patients were injected with one ampule Mofesal (650 mg mofebutazone sodium) i.m. The determination of mofebutazone in the plasma and in the synovial fluid was carried out by means of high performance liquid chromatography. The kinetics in the plasma and in the synovial fluid showed a dissociated course of development. Maximum concentrations of the active substance were reached after 1.4h in the plasma and after approx. 2 h in the synovial fluid. While mofebutazone in the plasma is eliminated with a half life time of 1.9 h, the half life time in the synovial fluid amounted to 7.7 h. According to pharmacokinetic simulation calculations no accumulation in the plasma occurred even after the administration of 1 ampule Mofesal three times daily, on the other hand a steady state is presumably reached in the synovia after 4-5 injections. On the basis of this study we regard it once again as essential that the kinetics in the synovial fluid should without doubt be preferred to the kinetics in the plasma for the calculation of a dosage schedule for non-steroidal antiphlogistics.

Adult↗