drotaverin and drotaverine--acephyllinate-drug-combination

Allometric scaling is an empirical examination of the relationships between the pharmacokinetic parameters and size (usually body weight, ratio of organ- and body weight, breathing number, etc.). Interspecies pharmacokinetics tend to approximate, the organism, as the sum of organs and tissues according to material balance. The allometric equations for the pharmacokinetic parameters were applied to scale the data with respect to pharmacokinetic time and remove the chronological time dependency. When the data of at least three species are available, the pharmacokinetic parameters can be fit according to body weight in log-log regression. Allometric scaling is not applicable in all cases, only when the selected species has similar physiological behaviour, such as protein-binding, metabolism, etc. Valuable information for the evaluation of the effect and the biopharmaceutical characteristics may emerge from more creative data analysis based on all result collected during the preclinical evaluation of a new drug. Author examined the applicability of the interspecies scaling method in the case of a new drug depogen, using drotaverin as reference. The pharmacokinetic data were collected from mouse, rat and dog and during the evaluation human data were applied too. The usual pharmacokinetic parameters were determined (MRT, MAT, beta, etc.), the results of allometric analysis were collected and the standard deviation of measured and calculated values were given.

Topics: Animals; Body Weight; Cats; Dogs; Drug Combinations; Humans; Mice; Organ Size; Papaverine; Parasympatholytics; Rats; Regression Analysis; Species Specificity; Theophylline; Tissue Distribution

Pentoxifylline is an orally active agent for the treatment of peripherial and cerebral vascular diseases. Pentoxifylline increases the deformability of red blood cells in vitro, reduces blood viscosity and decreases platelet aggregation and thrombus formation. Depogen has shown antiaggregatory effect both in vitro and in ex vivo. The inhibitory effect of Pentoxifylline was about 3-5 times weaker than that of Depogen. IC50 = 900/micrograms/ml for Depogén and 3600/micrograms/ml for Pentoxifylline on human platelet rich plasma. Depogen has shown ex vivo antiaggregatory effect on anesthetised rabbits, ID50 = 7 mg/kg in case of iv. administration, and ID50 = 300 mg/kg in case of orally administration. Both compound inhibit the release of platelet precoagulation factor, but the effect of Pentoxifylline was slighter.

Topics: Animals; Cell Aggregation; Drug Combinations; Drug Evaluation, Preclinical; Erythrocytes; Humans; Leukocytes; Papaverine; Pentoxifylline; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Factor 3; Rabbits; Theophylline

The absorption of Depogen was studied on an in vitro model and in various laboratory animals using stoichiometrically equivalent doses of drotaverin (No-Spa) calculated for drotaverin base for comparison. Blood levels of the drug were assessed by radiochemical and microchemical methods. Based on the results obtained and pharmacokinetic properties, the expectable optimal dosage and formulations for the possible field of indication were elaborated.

Topics: Animals; Biopharmaceutics; Diffusion; Dogs; Drug Combinations; Female; Male; Mice; Models, Biological; Papaverine; Rats; Theophylline

Topics: Animals; Chemical Phenomena; Chemistry; Dogs; Drug Combinations; Female; Gastric Emptying; Male; Papaverine; Parasympatholytics; Theophylline