PMID: 9647357Jul 1, 1998Paper

Pharmacokinetics and biodistribution of a nucleotide-based thrombin inhibitor in rats

Pharmaceutical Research
L Reyderman, S Stavchansky

Abstract

To characterize the pharmacokinetic and tissue distribution profiles of a nucleotide-based thrombin inhibitor (GS522, phosphodiester oligonucleotide, GGTTGGTGTGGTTGG) following intravenous administration to rats. Pharmacokinetic study: 10 mg/kg, 20 mg/kg, 30 mg/kg (6 animals/dose) were administered to rats by rapid injection into the femoral vein. Blood samples were collected over a 45 minute period. Plasma concentrations of GS522 were determined using capillary gel electrophoresis with laser-induced fluorescence detection. Biodistribution Study: 10 mg/kg (400 microl, 31.46 microCi/ml) of 3H-GS522 was administered to rats by rapid injection into the femoral vein. The animals were sacrificed by decapitation at 1, 5, 10, 30, 60, 360 minutes post-dose (3 rats/point). Brain, blood, duodenum, eyes, heart, kidney, liver, lungs, muscle, pancreas, skin, spleen and vein samples were collected, processed and quantitated using liquid scintillation counting. The pharmacokinetic profile declines in multiexponential manner, exhibiting extremely fast distribution and elimination (t1/2 = 7.6-9.0 min, Cl = 22.0-28.0 ml/min, V = 83.9-132.4 ml/kg). GS522 follows linear pharmacokinetics, with the area under the curve being proportional to the dose...Continue Reading

Citations

Sep 1, 2007·Expert Opinion on Drug Discovery·Aniela WochnerMartina Rimmele
Dec 24, 2014·Nucleic Acid Therapeutics·Katherine PerschbacherL James Maher
Jan 10, 2018·Frontiers in Pharmacology·Elena ZavyalovaGalina Pavlova
Jan 24, 2019·European Journal of Drug Metabolism and Pharmacokinetics·Hanna DavideitHardy Weisshoff
Jan 1, 2010·Biochemistry (Moscow) Supplement. Series B, Biomedical Chemistry·V A Spiridonova
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