Biomaterial Database

Pharmacokinetic disposition of the novel atypical anxiolytic CGS 9896 in the cynomolgus monkey. 1988

G M Kochak, and A Rakhit, and F Honc, and C J Mahoney

Development Department, CIBA-GEIGY Corporation, Ardsley, NY 10502.

The intravenous pharmacokinetic disposition of the novel, atypical anxiolytic CGS 9896 was studied in six cynomolgus monkeys. CGS 9896 was infused at dose levels of approximately 60, 120, and 240 micrograms/h/kg for a duration of 12 h, resulting in steady-state plasma concentrations averaging 38.4, 51.8, and 124 ng/ml, respectively. The average total systemic clearance was 35.3 ml/min/kg which was independent of dose and totally attributable to nonrenal pathways. The hepatic clearance was determined to be blood flow-rate dependent and the first-pass extraction calculated as approximately 84%. Both the apparent elimination rate constant and volume of distribution exhibited dose-dependent changes. Even though the plasma protein bound fraction was high (98.6%), no concentration dependency was observed. Furthermore, no concentration dependency was observed in the plasma/blood distribution ratio indicating the observed dose-related reduction in the volume of distribution may be attributable to nonlinear tissue uptake of CGS 9896.

UI	MeSH Term	Description	Entries
D007262	Infusions, Intravenous	The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.	Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008252	Macaca fascicularis	A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula.	Burmese Long-Tailed Macaque,Crab-Eating Monkey,Cynomolgus Monkey,M. f. aurea,M. fascicularis,Macaca fascicularis aurea,Monkey, Crab-Eating,Monkey, Cynomolgus,Crab-Eating Macaque,Burmese Long Tailed Macaque,Crab Eating Macaque,Crab Eating Monkey,Crab-Eating Macaques,Crab-Eating Monkeys,Cynomolgus Monkeys,Long-Tailed Macaque, Burmese,Macaque, Burmese Long-Tailed,Macaque, Crab-Eating,Monkey, Crab Eating
D008297	Male		Males
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011720	Pyrazoles	Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D001798	Blood Proteins	Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.	Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D006207	Half-Life	The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.	Halflife,Half Life,Half-Lifes,Halflifes
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia