Unexpected severe hepatotoxicity of ciprofloxacine: two case reports

Crozier, Alan; Koçoğlu, Hasan; Ersay, Ahmet Reşit; Ertung, Yunus; Kurt, Hasan

doi:10.3109/01480545.2010.495392

Cited by 15 publications

(7 citation statements)

References 10 publications

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“…In general ciprofloxacin is considered safe and is well tolerated [16–18], even in higher doses [5, 19]. Most common ADEs are mild; gastrointestinal reactions (nausea and diarrhoea), but CNS toxicity (anxiety, restlessness and seizures) occurs, as do skin reactions and hepatotoxicity [16–18, 20]. However, even at high dose seizures are rarely reported [18].…”

Section: Discussionmentioning

confidence: 99%

The ciprofloxacin target AUC : MIC ratio is not reached in hospitalized patients with the recommended dosing regimens

Haeseker

Stolk

Nieman

et al. 2012

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The efficacy target of AUC : MIC > 125 is based on the study of Forrest et al. in 1993. • Recent studies have shown that in ICU patients the ciprofloxacin efficacy target of AUC : MIC > 125 is often not reached. WHAT THIS STUDY ADDS • The efficacy targets of ciprofloxacin in patients in general wards are often not reached. Most patients have low AUC with current i.v. dosing regimens. We suggest increasing the standard dose of ciprofloxacin to 1200 mg intravenously 24 h–1. • Patients in general wards have high interindividual variability of pharmacokinetic parameters and therapeutic drug monitoring could be useful to support dosing. AIM The aim of this study was to determine the ciprofloxacin serum concentrations in hospitalized patients and to determine which percentage reached the efficacy target of AUC : MIC > 125. Additionally, the influence of demographic anthropomorphic and clinical parameters on the pharmacokinetics and pharmacodynamics of ciprofloxacin were investigated. METHODS In serum of 80 hospitalized patients ciprofloxacin concentrations were measured with reverse phase high performance liquid chromatography with fluorescence detection. The ciprofloxacin dose was 400–1200 mg day−1 i.v. in two or three doses depending on renal function and causative bacteria. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\PHARM 3.60). A two compartment open model was used. RESULTS Mean (± SD) age was 66 (± 17) years, the mean clearance corrected for bodyweight was 0.24 l h−1 kg−1 and the mean AUC was 49 mg l−1 h. Ciprofloxacin clearance and thus AUC were associated with both age and serum creatinine. Of all patients, 21% and 75% of the patients, did not reach the proposed ciprofloxacin AUC : MIC > 125 target with MICs of 0.25 and 0.5 mg l−1, respectively. A computer simulated increase in the daily dose from 800 mg to 1200 mg, decreased these percentages to 1% and 37%, respectively. CONCLUSION A substantial proportion of the hospitalized patients did not reach the target ciprofloxacin AUC : MIC and are suboptimally dosed with recommended doses. Taking into account the increasing resistance to ciprofloxacin worldwide, a ciprofloxacin dose of 1200 mg i.v. daily in patients with normal renal function is necessary to reach the targeted AUC : MIC > 125.

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Section: Discussionmentioning

confidence: 99%

The ciprofloxacin target AUC : MIC ratio is not reached in hospitalized patients with the recommended dosing regimens

Haeseker

Stolk

Nieman

et al. 2012

Brit J Clinical Pharma

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“…The tissue concentration generally exceeds serum concentration especially in genital tissuesincluding prostate. The drug is found in active form, in nasal and bronchial secretions, skin blister fluid, mucosa of the sinuses, sputum, saliva, lymph, prostatic secretions, peritoneal fluid and bile 9,10 . A deep analysis reveals the noticeable amounts of ciprofloxacin incartilage, and bones, fats, lungs, skin and skeletal muscles 11 , while less amount of drug has been detected in vitreous humor of the eyes 12 .This feature of deep penetration makes the use of this drug questionable in meat producing animals.…”

Section: Pharmacokinetic Properties Of Ciprofloxacinmentioning

confidence: 99%

Ciprofloxacin

Khan

Majeed

et al. 2015

TPMJ

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Fluoroquinolones are bactericidal agents that exhibit AUC/MIC dependentkilling. In general, they are effective against Gram-negative organisms and some mycobacteria.Ciprofloxacin is the members of this group and its bactericidal action involves the impeding ofenzyme topoisomerase II and IV. In human beings, this drug is recommended for a variety ofinfections including typhoid fever,chronic bacterial prostatitis, lower respiratory tract infections,skin infections, urinary tract infections, acute exacerbations of chronic bronchitis, complicatedintra-abdominal infections, infectious diarrhea, and uncomplicated cervical as well as urethralgonorrhea.The drug is as effective in animals as in humans, and is therefore used in animalsas well. According to European health law and National Office of Animal Health (NOAH), UK,the statutory withdrawal period for veterinary medicinal products must not be less than 28 daysfor meat from poultry. The chicken used for meat purpose usually is of the age between 6 to 8weeks, therefore the use of the drug must be discontinued by the age of 2 weeks. Whereas theage of chick at which it usually develops indicated diseases, is 3 weeks. In this situation, it is notpossible to attain a withdrawal period of 28 days. Based on these observations, ciprofloxacinuse may not be recommended in poultry for treatment of diseases as it may cause unnecessaryexposure to humans while utilizing poultry meat and may lead to the development of drugresistance.

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“…Cyclic voltammetric results and microscopic area calculation. The microscopic areas of the modied and the unmodied carbon paste electrode were obtained by the cyclic voltammetry using K 4 Fe(CN) 6 as a probe at different potential scan rates. For a reversible process, the following Randles-Sevcik formula is used:…”

Section: Ftir Spectroscopy Resultsmentioning

confidence: 99%

“…[2][3][4][5] An overdose of ciprooxacin results in severe hepatotoxicity. 6 Thus, it is essential to quantify CPFX in human plasma/serum/urine to monitor drug accumulation. CPFX analysis also plays a critical role in drug quality control.…”

Section: Introductionmentioning

confidence: 99%