| Effect of bile duct ligation and unilateral nephrectomy on brain concentration and convulsant potential of the quinolone antibacterial agent levofloxacin in rats. | |
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MedLine Citation:
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PMID: 8742326 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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K Akahane; S Ohkawara; M Nomura; M Kato |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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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:
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Created Date: 1996-10-01 Completed Date: 1996-10-01 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 8200838 Medline TA: Fundam Appl Toxicol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 280-6 Citation Subset: IM |
Affiliation:
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Drug Safety Research Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Anti-Infective Agents; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Phenylacetates; 51317-25-0/biphenylylacetic acid; 82419-36-1/Ofloxacin |
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