Pharmacokinetic and tissue analyses of levofloxacin in sheep (Ovis aries Linnaeus) after multiple-dose administration

Sartini, Irene; Łebkowska‐Wieruszewska, Beata; Kim, Tae Won; Lisowski, A.; Poapolathep, Amnart; Giorgi, Mario

doi:10.1016/j.rvsc.2019.11.008

Cited by 11 publications

(6 citation statements)

References 30 publications

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“…The Levofloxacin-treated group (Groups II and III) had significantly higher levels of urea and creatinine than the control group (Group I) and the vitamin D-treated group (Groups IV, V, VI) (p<0.05). Investigators identified the primary route of Levofloxacin excretion through the kidneys [ 46 ]. In addition, previous studies demonstrated that the administration of higher concentrations of Levofloxacin results in higher drug concentrations in plasma and urine and that at an acute and extremely toxic dose, the elimination of Levofloxacin is interrupted, increasing serum creatinine concentration, which is one of the biomarkers of renal failure.…”

Section: Discussionmentioning

confidence: 99%

Nephroprotective effect of vitamin D Against Levofloxacin-induced renal injury: an observational study

Mhaibes,

Abdul-Wahab

2023

JMedLife

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The pathogenesis of kidney damage involves complicated interactions between vascular endothelial and tubular cell destruction. Evidence has shown that vitamin D may have anti-inflammatory effects in several models of kidney damage. In this study, we evaluated the effects of synthetic vitamin D on levofloxacin-induced renal injury in rats. Forty-two white Albino rats were divided into six groups, with each group comprising seven rats. Group I served as the control (negative control) and received intraperitoneal injections of normal saline (0.5 ml) once daily for twenty-one days. Group II and Group III were treated with a single intraperitoneal dose of Levofloxacin (50 mg/kg/day) and (100 mg/kg/day), respectively, for 14 days (positive control groups). Group IV served as an additional negative control and received oral administration of vitamin D3 (500 IU/rat/day) for twenty-one days. In Group V, rats were orally administered vitamin D3 (500 IU/rat/day) for twenty-one days, and intraperitoneal injections of Levofloxacin (50 mg/kg/day) were administered on day 8 for 14 days. Group VI received oral vitamin D3 supplementation (500 IU/rat/day) for twenty-one days, followed by intraperitoneal injections of Levofloxacin (100 mg/kg/day) on day 8 for fourteen days. Blood samples were collected to measure creatinine, urea, malondialdehyde, glutathione reductase, and superoxide dismutase levels. Compared to the positive control group, vitamin D supplementation lowered creatinine, urea, and malondialdehyde levels, while increasing glutathione reductase and superoxide dismutase levels. Urea, creatinine, and malondialdehyde levels were significantly (p<0.05) higher in rats administered LFX 50mg and 100mg compared to rats given (LFX + vitamin D). The main findings of this study show that vitamin D reduces renal dysfunction, suggesting that vitamin D has antioxidant properties and may be used to prevent renal injury.

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Section: Discussionmentioning

confidence: 99%

Nephroprotective effect of vitamin D Against Levofloxacin-induced renal injury: an observational study

Mhaibes,

Abdul-Wahab

2023

JMedLife

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“…The oral bioavailabilities of LFX reported in humans are as follows: approximately 100% in a review article [ 58 ], or 69 ± 7% at a dose of 200 mg [ 59 ], approximately 70% and fecal recovery of LFX accounted for approximately 15% of an intravenous dose [ 60 ], 82 ± 13% in patients with AIDS at a dose of 500 mg [ 61 ], and 79 ± 47% at a dose of 250 mg in healthy volunteers [ 62 ]. In rats, approximately 90% of LFX dose was absorbed as the intact form from the intestinal tract into the portal system, and in sheep, the absolute oral bioavailability of LFX was 114 ± 27.7% at a dose of 2 mg/kg [ 63 ]. In mixed-breed dogs, the absolute oral bioavailability was 71.93 ± 9.75% at a dose of 5 mg/kg [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Development and Evaluation of EDTA-Treated Rabbits for Bioavailability Study of Chelating Drugs Using Levofloxacin, Ciprofloxacin, Hemiacetal Ester Prodrugs, and Tetracycline

et al. 2023

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Laboratory rabbits are fed foods rich with cationic metals, and while fasting cannot empty gastric contents because of their coprophagic habits. This implies that, in rabbits, the oral bioavailability of chelating drugs could be modulated by the slow gastric emptying rates and the interaction (chelation, adsorption) with gastric metals. In the present study, we tried to develop a rabbit model with low amounts of cationic metals in the stomach for preclinical oral bioavailability studies of chelating drugs. The elimination of gastric metals was achieved by preventing food intake and coprophagy and administering a low concentration of EDTA 2Na solution one day before experiments. Control rabbits were fasted but coprophagy was not prevented. The efficacy of rabbits treated with EDTA 2Na was evaluated by comparing the gastric contents, gastric metal contents and gastric pH between EDTA-treated and control rabbits. The treatment with more than 10 mL of 1 mg/mL EDTA 2Na solution decreased the amounts of gastric contents, cationic metals and gastric pH, without causing mucosal damage. The absolute oral bioavailabilities (mean values) of levofloxacin (LFX), ciprofloxacin (CFX) and tetracycline hydrochloride (TC), chelating antibiotics, were significantly higher in EDTA-treated rabbits than those in control rabbits as follows: 119.0 vs. 87.2%, 9.37 vs. 13.7%, and 4.90 vs. 2.59%, respectively. The oral bioavailabilities of these drugs were significantly decreased when Al(OH)3 was administered concomitantly in both control and EDTA-treated rabbits. In contrast, the absolute oral bioavailabilities of ethoxycarbonyl 1-ethyl hemiacetal ester (EHE) prodrugs of LFX and CFX (LFX-EHE, CFX-EHE), which are non-chelating prodrugs at least in in vitro condition, were comparable between control and EDTA-treated rabbits irrespective of the presence of Al(OH)3, although some variation was observed among rabbits. The oral bioavailabilities of LFX and CFX from their EHE prodrugs were comparable with LFX and CFX alone, respectively, even in the presence of Al(OH)3. In conclusion, LFX, CFX and TC exhibited higher oral bioavailabilities in EDTA-treated rabbits than in control rabbits, indicating that the oral bioavailabilities of these chelating drugs are reduced in untreated rabbits. In conclusion, EDTA-treated rabbits were found to exhibit low gastric contents including metals and low gastric pH, without causing mucosal damage. Ester prodrug of CFX was effective in preventing chelate formation with Al(OH)3 in vitro and in vivo, as well as in the case of ester prodrugs of LFX. EDTA-treated rabbits are expected to provide great advantages in preclinical oral bioavailability studies of various drugs and dosage formulations. However, a marked interspecies difference was still observed in the oral bioavailability of CFX and TC between EDTA-treated rabbits and humans, possibly due to the contribution of adsorptive interaction in rabbits. Further study is necessary to seek out the usefulness of the EDTA-treated rabbit with less gastric contents and metals as an experimental animal.

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“…Due to its pronounced effect against Gram-positive bacteria and certain pathogens, it is used to treat pneumonia, chronic bronchitis, skin inflammations, urinary tract infections, and other maladies [24]. LFX is also gaining interest in veterinary medicine, a common breeding ground for antibiotic resistance mechanisms [25][26][27]. It has been detected in wastewater, but also in river water [28] where it can severely affect aquatic microbial life and may promote antibiotic resistance in aquatic bacteria [29].…”

Section: Introductionmentioning

confidence: 99%

Sensing Levofloxacin with an RNA Aptamer as a Bioreceptor

Kramat,

Kraus,

Gunawan

et al. 2024

Biosensors

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To combat the growing threat of antibiotic resistance, environmental testing for antibiotic contamination is gaining an increasing role. This study aims to develop an easy-to-use assay for the detection of the fluoroquinolone antibiotic levofloxacin. Levofloxacin is used in human and veterinary medicine and has been detected in wastewater and river water. An RNA aptamer against levofloxacin was selected using RNA Capture-SELEX. The 73 nt long aptamer folds into three stems with a central three-way junction. It binds levofloxacin with a Kd of 6 µM and discriminates the closely related compound ciprofloxacin. Furthermore, the selection process was analyzed using a next-generation sequencing approach to better understand the sequence evolution throughout the selection. The aptamer was used as a bioreceptor for the development of a lateral flow assay. The biosensor exploited the innate characteristic of RNA Capture-SELEX to select aptamers that displace a complementary DNA oligonucleotide upon ligand binding. The lateral flow assay achieved a limit of visual detection of 100 µM. While the sensitivity of this assay constrains its immediate use in environmental testing, the present study can serve as a template for the selection of RNA aptamer-based biosensors.

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Pharmacokinetic and tissue analyses of levofloxacin in sheep (Ovis aries Linnaeus) after multiple-dose administration

Cited by 11 publications

References 30 publications

Nephroprotective effect of vitamin D Against Levofloxacin-induced renal injury: an observational study

Nephroprotective effect of vitamin D Against Levofloxacin-induced renal injury: an observational study

Development and Evaluation of EDTA-Treated Rabbits for Bioavailability Study of Chelating Drugs Using Levofloxacin, Ciprofloxacin, Hemiacetal Ester Prodrugs, and Tetracycline

Sensing Levofloxacin with an RNA Aptamer as a Bioreceptor

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