Biomaterial Database

Pharmacokinetics, absolute bioavailability, and disposition of [14C]nefazodone in the dog. 1993

U A Shukla, and P H Marathe, and K A Pittman, and R H Barbhaiya

Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Syracuse, NY 13221.

In a two-way crossover study, the pharmacokinetics and disposition of nefazodone (NEF) were investigated after intravenous (i.v.) infusion and oral (po) gavage of a solution of 10 mg/kg (5 microCi/kg) of [14C]NEF to four beagle dogs. Plasma was analyzed by HPLC for NEF, and its metabolites hydroxynefazodone (HO-NEF), m-chlorophenylpiperazine (mCPP), and p-hydroxynefazodone (p-HO-NEF). Plasma, urine, and feces were also analyzed for total radioactivity. Mean AUC(INF) values for NEF after po administration were about an order of magnitude lower compared with those after i.v. administration. Mean Cmax and AUC(INF) values for the metabolites after po administration were about as high or higher compared with those after i.v. administration. Mean (SD) total body clearance of NEF was 1.56 (0.34) liter/hr.kg-1, and mean (SD) steady-state volume of distribution of NEF was 3.24 (1.0) liter/kg. Mean (SD) absolute bioavailability of NEF after po administration was calculated to be 14.0 (4.2)%. The fraction of oral NEF eliminated presystemically was estimated to be 86%. Plasma concentration-time profiles for total radioactivity after i.v. and po administration were superimposable. The recovery of total radioactivity in urine and feces was similar after iv and po administration, indicating complete absorption of the drug after po administration. NEF, HO-NEF, and p-HO-NEF accounted for approximately 37% and 12% of the plasma AUC for total radioactivity following i.v. and po administration, respectively. The total urinary (28%) and fecal (61%) recovery after i.v. or po administration was approximately 90% of the dose within 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)

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
D008297	Male		Males
D010879	Piperazines	Compounds that are derived from PIPERAZINE.
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
D005243	Feces	Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
D000284	Administration, Oral	The giving of drugs, chemicals, or other substances by mouth.	Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
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
D000928	Antidepressive Agents	Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.	Antidepressant,Antidepressant Drug,Antidepressant Medication,Antidepressants,Antidepressive Agent,Thymoanaleptic,Thymoanaleptics,Thymoleptic,Thymoleptics,Antidepressant Drugs,Agent, Antidepressive,Drug, Antidepressant,Medication, Antidepressant
D001682	Biological Availability	The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.	Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D001711	Biotransformation	The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.