[Animal experiments on the pharmacokinetics of 4-amidinophenylpyruvic acid (APPA) (author's transl)].
The pharmacokinetics of the synthetic protease inhibitor APPA was studied in rabbits. After intravenous or oral application of 1 and 10 mg of (carboxyl-14C)-4-amidinophenylpyruvic acid hydrochloride/kg to rabbits, the plasma concentration was determined over several days and the excretion in urine during 24 hours. The course of the plasma concentration curves showed no dose-dependence of the pharmacokinetic behaviour. A three-phase course of the plasma concentration curves was observed after intravenous application, the slowest phase having a half-life of about 20 h. This very slow elimination is considered to be caused by tubular re-absorption of APPA. There is neither accumulation in organs, tissues or erythrocytes nor binding with plasma proteins. The thin-layer chromatographic analysis of the plasma revealed no labelled metabolites, but only unchanged APPA. APPA, when applied orally (in the form of an aqueous solution), is absorbed by more than 80%, the maximum plasma level being reached within 2--3 h. Intravenous and oral applications at 24-h intervals result in a cumulative increase in APPA concentration in the plasma. If APPA is applied to pregnant rabbits, it passes into the fetal circulation.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D007700:Kinetics; D010667:Phenylpyruvic Acids / Q000097:blood / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding; D011817:Rabbits; D013997:Time Factors; D014018:Tissue Distribution
D001798:Blood Proteins; D010667:Phenylpyruvic Acids
Tierexperimentelle Untersuchungen zur Pharmakokinetik von 4-Amidinophenylbrenztraubensäure (APPA).