The effect of thyme extract on beta2-receptors and mucociliary clearance.

UNLABELLED: Thyme is a broncholytic und secretomotoric agent. Thus, our aim was to investigate the influence of a thyme extract on beta (2)-receptors in competition binding experiments and relaxation experiments on rat uteri and trachea. Furthermore, the influence of the extract on respiratory clearance was of interest. Binding experiments were performed using purified rat lung membranes with the beta(2)-receptor ligand [(125)I]-CYP {[(125)I]-(+/-)-Iodocyanopindolol}. The transport of the fluorescence dye rhodamin 123 concerning ciliary action in the tracheal area of a mouse was investigated using a microdialysis technique. The thyme extract reduces only slightly [(125)I]-CYP binding and amplifies the displacement of [(125)I]-CYP by propranolol (non-specific beta-receptor antagonist): the displacement curve in the concentration range representing beta (2)-receptors (nM) is shifted to the left. Thyme extract had relaxing effects on organs possessing beta (2)-receptors (uterus and trachea). The propranolol-induced antagonism to isoprenaline is reverted concentration-dependently by the extract. A duplication of the rate of ciliary clearance by the extract was observed. IN CONCLUSION: 1) There is evidence for an influence of a thyme extract on beta (2)-receptors by both binding studies and biological effects: As can be derived from the shift of the propranolol displacement curve (nM), ingredients of the thyme extract slightly interact with beta (2)-receptors in rat lung tissue. This effect is indirect since no full range competition curve was reached. 2) An at least indirect interaction with beta (2)-receptors in rat uteri and trachea is revealed by a decreased antagonism of propranolol on the relaxing effect of isoprenaline by the plant extract. 3) An additional mechanism is presumed because at high extract concentrations isoprenaline-induced relaxation is complete, whereas the displacement of propranolol at beta (2)-receptors is only weak. 4) Thyme extract has an indirect (modulatory) effect on the beta (2)-receptor system. 5) Mucociliary clearance is improved in vivo. Its mechanism has still to be elucidated.

[Retard effect of acemetacin from a commercial preparation--kinetics in humans following single and multiple administration]. / Retardeffekt von Acemetacin aus einer handelsüblichen Zubereitung--Humankinetik nach Einzel- und Mehrfachapplikation.

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.