The effect of experimentally-induced renal failure on accumulation of bupropion and its major basic metabolites in plasma and brain of guinea pigs

C. Lindsay DeVane, Steven Laizure, Don F. Cameron

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Abstract

Dosage regimen adjustments because of poor renal function are often assumed to be unnecessary for extensively metabolized antidepressants. This assumption is being increasingly questioned in recognition of the role of active drug metabolites. The purpose of this study was to assess the steady-state accumulation of the new antidepressant bupropion and its three major basic metabolites in guinea pigs, with and without experimentally-induced renal guinea pigs, with and without experimentally-induced renal failure. Two groups of guinea pigs were treated by intraperitoneal (IP) implantation of mini-osmotic pumps containing bupropion hydrochloride. Immediately after surgery, one group of animals received an injection of uranyl nitrate. After 4 days, all animals were sacrificed by decapitation following blood removal by cardiac puncture. Analysis of plasma and brain samples by high performance liquid chromatography (HPLC) for concentrations of bupropion (BUP) and its major basic metabolites, the erythro-amino alcohol (EB), the threo-amino alocohol (TB) and the hydroxy metabolite (HB) revealed greater accumulation of BUP, TB, and HB in plasma and brain of the animals with renal failure compared to controls. No difference was found between groups in the concentrations of the EB metabolite. As the guinea pig shows a BUP and metabolite plasma concentration profile similar to that seen in human studies, these results suggest that further studies of bupropion and its major metabolites are warranted in patients with impaired renal function to assess possible excessive drug and metabolite accumulation.

Original languageEnglish (US)
Pages (from-to)404-408
Number of pages5
JournalPsychopharmacology
Volume89
Issue number4
DOIs
StatePublished - Jul 1 1986

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Bupropion
Renal Insufficiency
Guinea Pigs
Brain
Kidney
Antidepressive Agents
Uranyl Nitrate
Amino Alcohols
Decapitation
Punctures
Pharmaceutical Preparations
High Pressure Liquid Chromatography
Injections

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

The effect of experimentally-induced renal failure on accumulation of bupropion and its major basic metabolites in plasma and brain of guinea pigs. / Lindsay DeVane, C.; Laizure, Steven; Cameron, Don F.

In: Psychopharmacology, Vol. 89, No. 4, 01.07.1986, p. 404-408.

Research output: Contribution to journalArticle

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