Document Detail


Effect of bile duct ligation and unilateral nephrectomy on brain concentration and convulsant potential of the quinolone antibacterial agent levofloxacin in rats.
MedLine Citation:
PMID:  8742326     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To mimic the excretion route of the quinolone antibacterial agent levofloxacin (LVFX) in humans, we produced an excretion-limited (EL) model in male Sprague-Dawley rats by bile duct ligation and unilateral nephrectomy. We then examined the relationship between brain levels of LVFX and its convulsant effects in control and EL animals. Serum concentrations of LVFX in EL animals (EL + LVFX) were 2.38- and 1.59-fold and brain concentrations were 1.33- and 1.19-fold those of the controls (control + LVFX) at 30 min after a single intravenous injection of 10 and 100 mg/kg LVFX, respectively. Furthermore EL animals became more susceptible to the convulsant effect of LVFX with a 1.28-fold decrease in convulsion-inducing dose. In combination with oral pretreatment with 400 mg/kg 4-biphenylacetic acid (BPAA), convulsion-inducing doses in the control (control + LVFX + BPAA) and EL (EL + LVFX + BPAA) groups were markedly decreased by 2.25 and 9 times that of the control + LVFX group. EL operation and BPAA pretreatment slowed the elimination of LVFX in the serum and brain 4 hr later in the following order: EL + LVFX + BPAA, control + LVFX + BPAA, EL + LVFX, and control + LVFX groups. This order reflects that for the convulsion-inducing doses. These results suggest that EL rats may be a useful model for humans and that the convulsant effect of LVFX with or without BPAA arises not only from the attainment of maximum brain concentration but also from delayed disappearance from the brain.
Authors:
K Akahane; S Ohkawara; M Nomura; M Kato
Related Documents :
11861966 - Interaction between noise and asphyxiants: a concern for toxicology and occupational he...
7353566 - Interference effect of 3 hz brain stimulation on kindling behavior induced by 60 hz sti...
10819196 - Effects of chronic lead exposure on short-term and long-term depression in area ca1 of ...
22429366 - Alleviation of ferric chloride-induced seizures and retarded behaviour in epileptic rat...
3212056 - Sex differences in passive avoidance behavior of rats: sex-dependent susceptibility to ...
3577586 - Release of glucagon-like peptide 1 immunoreactivity from the perfused rat pancreas.
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Fundamental and applied toxicology : official journal of the Society of Toxicology     Volume:  29     ISSN:  0272-0590     ISO Abbreviation:  Fundam Appl Toxicol     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1996-10-01     Completed Date:  1996-10-01     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8200838     Medline TA:  Fundam Appl Toxicol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  280-6     Citation Subset:  IM    
Affiliation:
Drug Safety Research Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Anti-Infective Agents / blood,  metabolism,  toxicity*,  urine
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage,  toxicity
Bile Ducts / surgery
Brain / drug effects*,  metabolism
Dose-Response Relationship, Drug
Drug Synergism
Infusions, Intravenous
Injections, Intravenous
Ligation
Male
Nephrectomy / adverse effects
Ofloxacin / blood,  metabolism,  toxicity*,  urine
Phenylacetates / administration & dosage,  toxicity
Rats
Rats, Sprague-Dawley
Seizures / chemically induced*
Chemical
Reg. No./Substance:
0/Anti-Infective Agents; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Phenylacetates; 51317-25-0/biphenylylacetic acid; 82419-36-1/Ofloxacin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Biopersistence of man-made vitreous fibers and crocidolite asbestos in the rat lung following inhala...
Next Document:  Influence of oxygen partial pressure on human and mouse myeloid cell line characteristics.