Adverse Drug Interactions between Pyridonecarboxylic Acids and Nonsteroidal Antiinflammatory Drugs : Convulsion after Oral or Intracerebral Administration in Mice

Hirai, Shiro; Tánaka, Keiichi; Makino, Shinji; Narita, Hirokazu

doi:10.1248/yakushi1947.109.2_119

Cited by 15 publications

(5 citation statements)

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“…Convulsions have been reported in mice following the intracerebral administration of enoxacin and norfloxacin, but not ofloxacin and nalidixic acid (Hirai et al 1989). The convulsive threshold of these agents was greatly lowered by pretreatment with 4-biphenylacetic acid, a metabolite of fenbufen.…”

Section: Convulsionsmentioning

confidence: 99%

Clinical Features and Management of Adverse Effects of Quinolone Antibacterials

Paton

Reeves

1991

Drug Safety

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The quinolone antibacterials are proving very useful in the management of infection, notably for the treatment of Gram-negative bacteria. With the increasing use of these drugs, adverse effects are being recognised more often and careful documentation is still required. In general, the quinolones are of low toxicity. Gastrointestinal adverse effects are the most common, and are usually mild; indeed, all adverse events are generally mild and resolve on withdrawal of the offending drug. Certain precautions and contraindications are apparent. Because drug-induced arthropathies occur in juvenile animals, quinolones should not be administered to pregnant or lactating women or to growing children, unless the clinical benefit outweighs the risk. Caution should also be observed in patients with previous epilepsy or severe cerebral arteriosclerosis. Neurological effects may require the use of appropriate neuro- and psychoactive drugs, as well as the withdrawal of the precipitating agent. Hypersensitivity reactions to a fluoroquinolone may require the use of antihistamines, and in some cases topical or systemic steroids, and may well preclude future use of a fluoroquinolone. Dose adjustments may be necessary in patients with reduced renal function, when the measurement of serum concentrations may be desirable. Interstitial nephritis, haematuria and acute renal failure are rare effects of quinolone therapy which will require appropriate management including withdrawal of the precipitating drug. Interactions with theophylline and warfarin are of clinical significance, and may require plasma concentration monitoring and adjustment of dosage.

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Section: Convulsionsmentioning

confidence: 99%

Clinical Features and Management of Adverse Effects of Quinolone Antibacterials

Paton

Reeves

1991

Drug Safety

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“…However, undesirable adverse reactions and drug interactions have been reported following their use. In both man (Ministry of Health & Welfare 1986, 1989) and laboratory animals (Hirai et al 1989), their concomitant administration with the non-steroidal anti-inflammatory drug, fenbufen, has given rise to serious convulsions making it essential to elucidate the mechanism of the interaction between the drugs. Previously (Katagiri et al 1989a, b;Naora et al 1990a).…”

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confidence: 99%

A Possible Reduction in the Renal Clearance of Ciprofloxacin by Fenbufen in Rats

Naora

Katagiri

Ichikawa

et al. 1990

Journal of Pharmacy and Pharmacology

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The change in plasma concentration-time profile, serum protein binding and renal and biliary clearances of ciprofloxacin caused by coadministration of fenbufen has been studied in rats administered an intravenous dose of ciprofloxacin (5 mg kg-1) alone or with fenbufen (10 mg kg-1). Coadministered fenbufen significantly prolonged the plasma elimination half-life of ciprofloxacin from 40.5 to 57.6 min and tended to reduce the total body clearance of this quinolone by about 20%. The extent of ciprofloxacin binding to rat serum protein was not affected by fenbufen, nor did it affect the biliary clearance of the quinolone. However, fenbufen tended to reduce renal clearance and significantly decreased the cumulative renal excretion of the quinolone during at least the first 3 h after drug administration. These results suggest a possible reduction of ciprofloxacin clearance owing to inhibition of renal excretion by fenbufen.

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“…GABA and muscimol had no effect on convulsions induced by either quinolone. weak convulsive activities (5,7,13,19,23). The LVFX used in this study is the S-(-)-isomer of OFLX and has acute toxicity and convulsive activity similar to those of OFLX in mice after i.v.…”

Section: Methodsmentioning

confidence: 95%

“…However, no difference in metabolism and the concentration of other quinolones, including OFLX, in tissue, between administration of a quinolone alone and a quinolone plus an NSAID has been reported (13,40).…”

Section: Quinolone-induced Convulsions In Mice 1769mentioning

confidence: 99%

Involvement of inhibitory and excitatory neurotransmitters in levofloxacin- and ciprofloxacin-induced convulsions in mice

Akahane

Kato

Takayama

1993

Antimicrob Agents Chemother

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We studied the effects of 'y-aminobutyric acid (GABA)-benzodiazepine receptor agonists and glutamate receptor antagonists on levofloxacin (LVFX)-and ciprofloxacin (CPFX)-induced convulsions using intrathecal (i.t.) injections in mice. We also studied the effects of these agonists and antagonists on exacerbated convulsions induced by coadministration of the quinolone with 4-biphenylacetic acid (BPAA). The agonists or antagonists were injected i.t. 5 min and BPAA was administered orally 30 min before a single i.t. injection of the quinolone (10 pl per animal). The animals were observed for clonic convulsion and death, and latency times to the appearance of convulsion were determined. Among the agonists, baclofen showed marked inhibition of both LVFX-and CPFX-induced convulsions, while other compounds such as GABA, muscimol, diazepam, and 3-aminopropylphosphonic acid had slight effects. Among the antagonists, kynurenic acid showed the strongest inhibition of convulsions caused by all doses of LVFX and CPFX and prolonged latency times; 'y-glutamylaminomethylsulfonic acid (GAMS) also markedly inhibited convulsions. The antagonists D-AP-5, AP-7, and 6,7-dinitroquinoxaline-2,3-dione (DNQX) had slight effects. Additionally, GAMS, DNQX, and MK-801 significantly lowered the incidence of death in the groups treated with CPFX. The enhanced convulsive activities of LVFX or CPFX by pretreatment with BPAA were clearly blocked by baclofen, kynurenic acid, GAMS, and DNQX. D-AP-5 and AP-7 also showed clear effects on the activity of LVFX. These results suggest that LVFX has fewer effects on the brain than CPFX and that convulsions induced by these quinolones alone and by these quinolones administered with BPAA may be mediated largely through glutamate and GABAB rather than GABAA receptors in mice.Because of their excellent activities, quinolone antibacterial agents have been widely adopted for use in clinical practice. Although recently developed quinolones are less toxic than earlier compounds, they still produce very few incidences of various adverse effects on the central nervous system. Among these, convulsions remain a serious problem; enoxacin (ENX) (29), norfloxacin (NFLX) (2, 39), and ciprofloxacin (CPFX) (3) have been reported to induce convulsions in humans. Furthermore, these convulsions have been reported to be enhanced by coadministration with nonsteroidal anti-inflammatory drugs (NSAIDs) (2,3,29,31). The mechanisms underlying these convulsions have therefore been investigated in animal models.It (1, 6, 14, 26-28, 33, 40). Moreover, their enhanced convulsive activity in the presence of NSAIDs is thought to be mediated through the augmentation of interactions between quinolones and GABAA by NSAIDs, as evidenced by electrophysiological studies (10, 18) and binding assays (7). In contrast, other studies have reported the failure of GABA-benzodiazepinergic drugs to inhibit completely convulsions caused by coadministration of a quinolone and an NSAID (11,20,30,31), the lack of any clear correlation between the activitie...

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Adverse Drug Interactions between Pyridonecarboxylic Acids and Nonsteroidal Antiinflammatory Drugs : Convulsion after Oral or Intracerebral Administration in Mice

Cited by 15 publications

References 0 publications

Clinical Features and Management of Adverse Effects of Quinolone Antibacterials

Clinical Features and Management of Adverse Effects of Quinolone Antibacterials

A Possible Reduction in the Renal Clearance of Ciprofloxacin by Fenbufen in Rats

Involvement of inhibitory and excitatory neurotransmitters in levofloxacin- and ciprofloxacin-induced convulsions in mice

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