Search

Silymarin, the active principle of the Milk Thistle (Silybum marianum Gaertner), is a very potent inhibitor of cyclic AMP breakdown in vitro by a commercial beef heart phosphodiesterase preparation. Its main constituents, silybin, silydianin and silychristin, are 12.66 to 52.06 times more active than theophylline and 0.77 to 3.17 times more active than papaverine in this respect. Using a novel HPLC technique, the enzyme kinetical analysis can be performed much faster than by the classical methods.

The intercalation of thalidomide (alpha-phthalimidoglutarimide) into nucleic acids was studied by spectrophotometric titrations, displacement of known intercalators, viscosity changes of DNA solutions, and by phase partition analysis. Specific binding of thalidomide was found to DNA of various specimens (human placenta, calf thymus, salmon sperm), but not to RNA (from bakers yeast, torula yeast).

The official dissolution apparatuses of the U.S.P. XXI or those recommended by the DAC 1979, respectively, are not suitable for the pertinent examination of rectal drug dosage forms. In the literature, on the other hand, numerous experimental setups have been proposed for the study of drug release from suppositories. However, these devices are all rather complicated as concerned with their construction as well as their handling, and, thus, cannot be considered as universally applicable test models. The rotating flask model, that has already been presented to the public earlier, in its two appearances, i.e. the dissolution tester (simple rotating flask) and the absorption model (compartmented rotating flask), can be employed for the testing of drug liberation from suppositories. The release parameters which have been determined in either of the two types of the rotating flask correlate well with each other and are also relevant characteristics of the bioavailability.

Rosmarinic acid (RA) is a nonsteroidal anti-inflammatory agent. The purpose of the study was to investigate the transdermal absorption of RA, its tissue distribution and absolute bioavailability. In ex vivo experiments, permeation of RA across excised rat skin was about 8 times higher from alcoholic solution than from water, indicating that ethanol may act as sorption promoter. The flux from water or alcoholic solution was 4.4 or 10 micrograms/cm2/h, and the tleg was 7.8 or 3.7 h, respectively. After I.V. administration, RA is best described by a 2-compartment open model; t1/2 = 1.8 h, t1/2 alpha = 0.07 h, V tau = 2.3 L/kg, V beta = 15.3 L/kg. Upon topical administration of RA in form of a W/O ointment (25 mg/kg, 50 cm2), the absolute bioavailability was 60%. 0.5 hours after I.V. administration, RA was detected and measured in brain, heart, liver, lung, muscle, spleen and bone tissue, showing the highest concentration in lung tissue (13 times the blood concentration), followed by spleen, heart and liver tissue. 4.5 hours (peak time) after topical administration of about 3 mg on the hind leg over 20 cm2, RA was measured in blood, skin, muscle and bone tissue. The percutaneous route of administration seems to be a promising one for the therapeutic use of RA as nonsteroidal anti-inflammatory agent.