ABSTRACT
The levels of himantane and its metabolites in daily urine and feces of rats were measured after intraperitoneal and oral dose of 25 mg/kg. The injected dose of the initial substance and 1.3% its metabolites were eliminated with excrements within 24 h after administration via both routes 0.23%.
Subject(s)
Adamantane/analogs & derivatives , Antiparkinson Agents/metabolism , Antiparkinson Agents/pharmacokinetics , Adamantane/administration & dosage , Adamantane/metabolism , Adamantane/pharmacokinetics , Adamantane/urine , Administration, Oral , Animals , Antiparkinson Agents/administration & dosage , Antiparkinson Agents/urine , Biotransformation , Feces/chemistry , Injections, Intraperitoneal , Mass Spectrometry , Rats , Time FactorsABSTRACT
Pharmacokinetic parameters of himantane and its metabolites in the blood plasma of rabbits were compared after single administration of himantane solution in a dose of 25 mg intravenously and 100 mg orally. It was established that the original substance is characterized by low absolute bioavailability (7.95%). Himantane is subjected to first-pass effect and is extensively metabolized in the liver to metabolites with m/z 266 and 250.
Subject(s)
Adamantane/analogs & derivatives , Adamantane/administration & dosage , Adamantane/blood , Adamantane/metabolism , Adamantane/pharmacokinetics , Administration, Oral , Animals , Biological Availability , Cross-Over Studies , Injections, Intravenous , Liver/drug effects , Liver/metabolism , Male , RabbitsABSTRACT
The pharmacokinetics ofhemantane after administration in different ways has been studied in rats. It is established that hemantane introduced both orally (p.o.) and intravenously (i.v.) is very intensively metabolized, with the main metabolites characterized by m/z = 250 and 266 and detected for 6 hours after the administration in both ways. Hemantane shows high rate of permeability into its target organ--brain--whereas the permeation of its metabolites is extremely low. The absolute bioavailability ofhemantane upon p.o. administration was 14.1%. The substance is subject to the "first-pass effect". The unchanged substance was determined in daily urine and feces in very small fractions of the administered dose: 0.23% in urine and 0.08% in feces after i.v. administration and 0.02% in feces after p.o. administration. Thus, it may be concluded that the substance is completely absorbed in rats from the gastro-intestinal tract into systemic blood circulation.
