Biomaterial Database

Disposition of MK-852, a fibrinogen receptor antagonist, in rats and dogs. 1994

S Vickers, and C A Duncan, and A S Yuan, and K P Vyas

Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486.

MK-852, an antagonist of the platelet fibrinogen receptor GPIIb/IIIa, is the cyclic disulfide N-acetyl-cys-asn-(5,5-dimethyl-4-thiazolidine-carbonyl)- (4-aminomethyl-phe)-gly-asp-cys, monoacetate (all L-amino acids). Radiolabeled MK-852 was synthesized with either a 3H label in the N-acetyl group of the cystine residue or a 14C label in the aminomethyl group. Plasma concentrations of unchanged MK-852 in five rats declined with a mean terminal half-life of 0.92 hr after a 2.5 mg/kg i.v. dose of MK-852; plasma clearance and Vd were 23.1 ml/min/kg and 1.81 liters/kg, respectively. More label was excreted in urine (74-76%) than in feces (7-15%) when either [3H]MK-852 or [14C]MK-852 was given intravenously to groups of four rats (2.5 mg/kg). High concentrations of 3H in rat kidney were consistent with high renal clearance of MK-852, and MK-852 accounted for virtually all of the urinary 3H (and 14C) label. Following a 0.6 mg/kg i.v. dose, the half-life, plasma clearance, and Vd of MK-852 in four dogs were 0.84 hr, 3.93 ml/min/kg, and 0.28 liters/kg, respectively. In dogs, the excretion patterns of radioactivity were similar to those of rats, except that 14C urinary recoveries (79%) were higher than 3H (63%). Unchanged MK-852 represented essentially all of the urinary 3H label. Fractionation of dog 14C urinary radioactivity yielded one major and several minor polar labeled species. The major species was unchanged [14C]MK-852 (quantitated by radioimmunoassay as approximately 80% of the label).(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009842	Oligopeptides	Peptides composed of between two and twelve amino acids.	Oligopeptide
D010456	Peptides, Cyclic	Peptides whose amino acid residues are linked together forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS; some are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).	Circular Peptide,Cyclic Peptide,Cyclic Peptides,Cyclopeptide,Orbitide,Circular Peptides,Cyclopeptides,Orbitides,Peptide, Circular,Peptide, Cyclic,Peptides, Circular
D010649	Phenylalanine	An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.	Endorphenyl,L-Phenylalanine,Phenylalanine, L-Isomer,L-Isomer Phenylalanine,Phenylalanine, L Isomer
D010975	Platelet Aggregation Inhibitors	Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.	Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D010980	Platelet Membrane Glycoproteins	Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.	PM-GP,Platelet Glycoprotein,Platelet Membrane Glycoprotein,PM-GPs,Platelet Glycoproteins,Glycoprotein, Platelet,Glycoprotein, Platelet Membrane,Glycoproteins, Platelet,Glycoproteins, Platelet Membrane,Membrane Glycoprotein, Platelet,Membrane Glycoproteins, Platelet,PM GP
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
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
D002250	Carbon Radioisotopes	Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.	Radioisotopes, Carbon