Biomaterial Database

Coadministration of nefazodone and benzodiazepines: IV. A pharmacokinetic interaction study with lorazepam. 1995

D S Greene, and D E Salazar, and R C Dockens, and P Kroboth, and R H Barbhaiya

Department of Metabolism, Bristol-Myers Squibb Company, Princeton, New Jersey 08543-4000, USA.

This study was conducted to determine the potential for an interaction between nefazodone (NEF), a new antidepressant, and lorazepam (LOR) after single- and multiple-dose administration in a randomized, double-blind, parallel-group, placebo-controlled study in healthy male volunteers. A total of 12 subjects per group received either placebo (PLA) twice daily, 2 mg of LOR twice daily, 200 mg of NEF twice daily, or the combination of 2 mg of LOR and 200 mg of NEF (LOR+NEF) twice daily for 7 days. Plasma samples were collected after dosing on day 1 and day 7 and before the morning dose on days 4, 5, and 6 for the determination of LOR, NEF, and NEF metabolites hydroxy (HO)-NEF, m-chlorophenylpiperazine (mCPP), and dione by validated high-performance liquid chromatography methods. Steady-state levels in plasma were reached by day 4 for LOR, NEF, HO-NEF, mCPP, and dione. Noncompartmental pharmacokinetic analysis showed that there was no effect of LOR on the single dose or steady-state pharmacokinetics of NEF, HO-NEF, or dione after coadministration. The steady-state mCPP Cmax values decreased 36% for the LOR+NEF group in comparison to that when NEF was given alone. There was no effect of NEF on the pharmacokinetics of LOR after coadministration. The absence of an interaction appears to be attributable to LOR's metabolic clearance being dependant on conjugation rather than hydroxylation. Overall, no change in LOR or NEF dosage is necessary when the two drugs are coadministered.

UI	MeSH Term	Description	Entries
D008140	Lorazepam	A benzodiazepine used as an anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent.	Apo-Lorazepam,Ativan,Donix,Duralozam,Durazolam,Idalprem,Laubeel,Lorazep Von Ct,Lorazepam Medical,Lorazepam-Neuraxpharm,Lorazepam-Ratiopharm,Novo-Lorazem,Nu-Loraz,Orfidal Wyeth,Sedicepan,Sinestron,Somagerol,Temesta,Tolid,Témesta,WY-4036,Apo Lorazepam,Lorazepam Neuraxpharm,Lorazepam Ratiopharm,Medical, Lorazepam,Novo Lorazem,Nu Loraz,Von Ct, Lorazep,WY 4036,WY4036,Wyeth, Orfidal
D008297	Male		Males
D010879	Piperazines	Compounds that are derived from PIPERAZINE.
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004334	Drug Administration Schedule	Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.	Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D004359	Drug Therapy, Combination	Therapy with two or more separate preparations given for a combined effect.	Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
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