Serum and sputum concentrations of enoxacin after single oral dosing in a clinical and bacteriological study

Davies, B. I.; Maesen, F. P. V.; Teengs, J. P.

doi:10.1093/jac/14.suppl_c.83

Cited by 61 publications

(29 citation statements)

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“…In some of these patients, this interaction gave rise to signs and symptoms of theophylline toxicity (Davies et al, 1984;Wijnands et al, 1985a). The present study confirms this interaction in subjects with stable pulmonary disease, whose only simultaneous treat-…”

Section: Resultssupporting

confidence: 82%

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The influence of quinolone derivatives on theophylline clearance.

Wijnands¹,

Vree²,

Herwaarden³

1986

Brit J Clinical Pharma

242

118

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1 Enoxacin decreases the metabolic clearance of the bronchodilator theophylline not only in severely ill patients, but also in patients with stable chronic obstructive airways disease.2 In this comparative study, significantly increased plasma theophylline concentrations were measured during co-administration of enoxacin (110.9%) and, to a lesser degree, also during co-administration of pefloxacin (19.6%) and ciprofloxacin (22.8%). 3 Total body clearance of theophylline was significantly decreased by enoxacin (63.6%), ciprofloxacin (30.4%) and pefloxacin (29.4%). The pharmacokinetic parameters of theophylline did not change during co-administration of ofloxacin and nalidixic acid. 4 There is growing evidence that the observed interaction is caused not by the parent drugs, but by the 4-oxo metabolite of enoxacin, pefloxacin and ciprofloxacin.Keywords quinolone 4-oxo quinolone enoxacin pefloxacin ciprofloxacin ofloxacin nalidixic acid theophylline interaction lower respiratory tract infections

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Section: Resultssupporting

confidence: 82%

“…These high theophylline concentrations resulted in severe complaints of nausea, vomiting, tachycardia or agitation for some of the patients (Wijnands et al, 1984;Davies et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

The influence of quinolone derivatives on theophylline clearance.

Wijnands¹,

Vree²,

Herwaarden³

1986

Brit J Clinical Pharma

242

118

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“…The increase in plasma theophylline concentration appeared to be independent of enoxacin dose (800-1200 mg day-'). Davies et al (1984) Time after last theophylline dose (h) Figure 2 Elimination of theophylline in a single patient during enoxacin treatment (0) and 1 week after enoxacin had been stopped (-).…”

Section: Discussionmentioning

confidence: 99%

“…Simultaneous treatment with drugs such as allopurinol (Manfredi & Vesell, 1981), cimetidine (Jackson et al, 1981;Reitberg et al, 1981), erythromycin (Prince et al, 1981), troleandomycin (Weinberger et al, 1977), can cause decreased theophylline clearance, whereas coadministration of phenobarbitone (Landay et al, 1978), phenytoin (Marquis et al, 1982) and isoprenaline (Hemstreet et al, 1982) In a previous study with enoxacin in respiratory tract infections by Davies et al (1984), the drug had to be discontinued in 9 of 15 patients because of side effects mainly related to the digestive system; seven of these patients used concomitant theophylline medication. In a clinical study with oral enoxacin in patients with a respiratory tract infection we observed unexpectedly high plasma theophylline concentrations causing complaints and symptoms of theophylline toxicity such as nausea and vomiting (Wijnands et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Enoxacin decreases the clearance of theophylline in man.

Wijnands¹,

Vree²,

Herwaarden³

1985

Brit J Clinical Pharma

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In patients treated concurrently with theophylline and enoxacin, a new broad‐spectrum antibacterial agent of the quinolone class, unexpectedly high plasma theophylline concentrations were measured. In part I of this study, daily plasma theophylline concentrations were measured in 14 patients. The mean +/‐ s.d. theophylline concentrations increased from 8.5 +/‐ 2.8 micrograms ml‐1 prior to enoxacin to a maximum of 21.7 +/‐ 7.8 micrograms ml‐1 during coadministration. In part II, six of these patients received aminophylline intravenously at a constant infusion rate and under controlled conditions. Plasma theophylline concentrations rose from 8.4 +/‐ 2.4 micrograms ml‐1 prior to enoxacin treatment to 15.0 +/‐ 5.1 micrograms ml‐1 at day 3 of coadministration (P less than 0.005). Plasma protein‐binding and renal clearance of theophylline remained unchanged, whereas total body clearance of theophylline significantly decreased (P less than 0.005). From these observations it is concluded that the rise of plasma theophylline concentrations is caused by a reduced metabolic clearance of theophylline. If concomitant use of both drugs is necessary, monitoring of plasma theophylline concentration and adjustment of the theophylline dose is recommended.

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“…The MICs of enoxacin and norfloxacin for new colonizing microorganisms were determined by an agar dilution method. Breakpoints of 2.0 mg/liter for enoxacin and of 0.5 mg/liter for norfloxacin were chosen on the basis of previous pharmacokinetic studies (1,8,16).No enoxacin or norfloxacin activity was found in any fecal specimen obtained pretreatment or on day 21. The mean concentration of enoxacin on day 7 was 350 mg/kg of feces (range, 100 to 500 mg/kg), and the mean concentration of norfloxacin on day 7 was 950 mg/kg of feces (range, 440 to …”

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confidence: 99%

Comparative effects of enoxacin and norfloxacin on human colonic microflora

Edlund

Lidbeck

Kager

et al. 1987

Antimicrob Agents Chemother

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Ten healthy volunteers received 400 mg of enoxacin and another ten healthy volunteers received 200 mg of norfloxacin orally twice a day for 7 days. Fecal specimens were collected before, during, and after drug administration to study the impact of enoxacin and norfloxacin on the normal colonic microflora. On day 7, the mean concentrations of enoxacin abd norfloxacin were 350 and 950 mg/kg of feces, respectively. Enoxacin and norfloxacin affected the colonic microfloral in similar ways. The number of strains of the family Enterobacteriaceae was markedly suppressed during drug administration, whereas the gram-positive and anaerobic microfioras were not significantly altered. Two weeks after withdrawal of the drugs, the colonic microflora had returned to normal.Enoxacin and norfloxacin are members of the 4-quinolone group of antimicrobial agents, whose in vitro activity is primarily directed against a broad spectrum of aerobic gram-negative bacteria, including members of the family Enterobacteriaceae and Pseudomonas aeruginosa (3,6,12). Enoxacin and norfloxacin have moderate activities against gram-positive microorganisms, such as staphylococci and stteptococci; anaerobic bacteria are generally resistant. The 4-quinolones may be used in prophylactic and suppressive long-term treatment, i.e., in urological surgery or complicated urinary tract infections, and for selective decontamination of the gut in immunocompromised patients (10,13,15). Treatment with antimicrobial agents can induce undesited changes in the gastrointestinal microflora (11), and it is therefore of clinical interest to investigate the effect of new agents on such microflora. In this article, the effects on the colonic microflora of enoxacin and norfloxacin in human volunteers are described.Twenty healthy volunteers participated in the study. None of them had received any antimicrobial agent during the 3 weeks before the investigation. The study was approved by the Local Ethics Committee of Karolinska Institute, Stockholm, Sweden. No other medication except oral contraceptives was allowed during the investigation period.In the enoxacin group, five females and five males (median age, 33 years; range, 37 to 64 years) received 400 mg of enoxacin (supplied by Warner-Lambert Co., Morris Plains, N.J.) perorally twice a day for 7 days. The tablets were taken with 100 ml of water just before meals. Stool specimens were collected in sterile plastic containers before the administration period (day 0) and on days 2, 4, 7, 9, 11, 16, and 21. In the norfloxacin group, five femnales and five males (median age, 30 years; range, 24 to 37 years) received 200 mg of norfloxacin (supplied by Astra Lakemedel AB, Sodertalje, Sweden) perorally twice a day for 7 days. The tablets were administered before meals with 100 ml of water. Stool specimens were collected in sterile plastic containers on days 0, 3, 5, 7, 14, and 21. All fecal specimens were stored at -70°C until assayed.The fecal concentrations of enoxacin and norfloxacin were assayed by the agar well diffusion meth...

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Serum and sputum concentrations of enoxacin after single oral dosing in a clinical and bacteriological study

Cited by 61 publications

References 0 publications

The influence of quinolone derivatives on theophylline clearance.

The influence of quinolone derivatives on theophylline clearance.

Enoxacin decreases the clearance of theophylline in man.

Comparative effects of enoxacin and norfloxacin on human colonic microflora

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