Biomaterial Database

Pharmacokinetics of nordiazepam in physical dependence and precipitated abstinence in dogs. 1993

E P Wala, and W R Martin, and J W Sloan

Department of Anesthesiology, University of Kentucky, Lexington 40536-0216.

Previous studies suggested that the extensive accumulation of benzodiazepines is an important factor in the induction of physical dependence. The mechanistic basis for accumulation of nordiazepam (ND) and its metabolite, oxazepam (OX), have been examined in crossover studies in drug-naive and in ND-dependent dogs that exhibited a flumazenil-precipitated abstinence syndrome. ND and parent OX have similar pharmacokinetic profiles. Steady-state plasma levels of ND and OX cannot be predicted from single-dose pharmacokinetics. Reduced plasma clearance of ND and altered plasma protein binding were observed in dogs physically dependent upon ND. The benzodiazepine antagonist, flumazenil, significantly reduces steady-state plasma levels of total and free ND.

UI	MeSH Term	Description	Entries
D007275	Injections, Intravenous	Injections made into a vein for therapeutic or experimental purposes.	Intravenous Injections,Injection, Intravenous,Intravenous Injection
D010076	Oxazepam	A benzodiazepine used in the treatment of anxiety, alcohol withdrawal, and insomnia.	Adumbran,Serax,Tazepam
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
D003708	Nordazepam	An intermediate in the metabolism of DIAZEPAM to OXAZEPAM. It may have actions similar to those of diazepam.	Dealkylprazepam,Demethyldiazepam,Deoxydemoxepam,Desmethyldiazepam,Nordiazepam,Calmday,N-Desalkylhalazepam,N-Descyclopropylmethyl-Prazepam,N-Descyclopropylmethylprazepam,N-Destrifluoroethylhalazepam,Nordaz,Norprazepam,Ro 5-2180,Tranxilium N,Vegesan,N Desalkylhalazepam,N Descyclopropylmethyl Prazepam,N Descyclopropylmethylprazepam,N Destrifluoroethylhalazepam,Ro 5 2180,Ro 52180
D003975	Diazepam	A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.	7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D005260	Female		Females
D005442	Flumazenil	A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.	Flumazepil,Anexate,Lanexat,Ro 15-1788,Romazicon,Ro 15 1788,Ro 151788
D006868	Hydrolysis	The process of cleaving a chemical compound by the addition of a molecule of water.