Effects of Aluminium-Containing Antacid on Bioavailability of Ofloxacin Following Oral Administration of Pivaloyloxymethyl Ester of Ofloxacin as Prodrug.

Maeda, Yorinobu; Omoda, Kei; Konishi, Toshio; Takahashi, Makoto; Kihira, Kenji; Hibino, Satoshi; Tsukiai, Satsuki

doi:10.1248/bpb.16.594

Cited by 9 publications

(5 citation statements)

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“…In an everted sac investigation, cyclacillin (1‐amino‐cyclohexyl penicillin) was transported actively but the other amino penicillins (amoxicillin and ampicillin) were transported passively [120] . In an everted sac experiment, the pivaloyloxymethyl ester of ofloxacin was efficiently absorbed even in the presence of aluminium ions, whereas the absorption of ofloxacin was decreased significantly by the presence of aluminium ions; the findings were confirmed through in‐vivo results [121] . The site and step of isomeric inversion can be investigated through the present model.…”

Section: Applicationsmentioning

confidence: 65%

Everted gut sac model as a tool in pharmaceutical research: limitations and applications

Alam

Al-Jenoobi

Al-Mohizea

2011

Journal of Pharmacy and Pharmacology

157

108

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Objectives This review discusses the limitations and applications of the everted gut sac model in studying drug absorption, metabolism, and interaction. Key findings The mechanism of drug absorption, interaction and the effect of factors such as age, sex, species, chronic therapy, and disease state on drug absorption have been summarized. The experimental conditions and their effects on the outcomes of trials have been discussed also. Summary The everted sac model is an efficient tool for studying in-vitro drug absorption mechanisms, intestinal metabolism of drugs, role of transporter in drug absorption, and for investigating the role of intestinal enzymes during drug transport through the intestine.

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Section: Applicationsmentioning

confidence: 65%

Everted gut sac model as a tool in pharmaceutical research: limitations and applications

Alam

Al-Jenoobi

Al-Mohizea

2011

Journal of Pharmacy and Pharmacology

157

108

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“…Chelate formation using oxygen in a carboxylic acid at the 3-position and carbonyl oxygen atom at the 4-position of quinolones is reported in many articles [ 70 , 71 , 72 , 73 ]. Various ester prodrugs of LFX including LFX-EHE prevented chelate formation possibly by steric hindrance of the binding site in vitro and in vivo [ 31 , 32 , 33 , 74 ]. In addition to chelate formation in water, quinolones also interact with cationic metal-containing solid materials by physicochemical adsorption [ 15 , 29 , 75 , 76 , 77 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the addition of ester moiety at the carboxyl acid of CFX was thought to inhibit the binding of metal cations by steric hindrance. Many other ester prodrugs of CFX are also expected to inhibit the chelate formation of CFX as observed with LFX ester prodrugs and CFX-EHE [ 32 , 33 , 70 , 74 ]. Regarding the adsorptive interaction of CFX, it was reported that when various antibiotics were incubated in soil-water slurries (silt-loam, sand-loam, and sand; 20 w / v % soil), β-lactams and florfenicol antibiotics remain bioactive in soils while CFX, neomycin, and TC were neutralized [ 52 ].…”

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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“…Alguns pró-fármacos de fluorquinolonas encontram-se descritos na literatura (ERTAN et al, 1992;MAEDA et al, 1993;DOBIAS et al, 1995;PANDEYA et al, 2000;PANDEYA et al, 2001;BAKER et al, 2004). Porém, o planejamento de prófármacos antimicobacterianos de fluorquinolonas é ainda pouco explorado.…”

Section: Ensaio Biológico Preliminar In Vitrounclassified

“…MAEDA et al (1993) relataram a síntese do éster pivaloiloximetílico do ofloxacino, como o objetivo de avaliar a biodisponibilidade do fármaco após a administração concomitante de antiácidos contendo alumínio. A síntese se procedeu…”

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Síntese e atividade antimicobacteriana de ésteres do ácido pirazinóico e quinolonas

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Effects of Aluminium-Containing Antacid on Bioavailability of Ofloxacin Following Oral Administration of Pivaloyloxymethyl Ester of Ofloxacin as Prodrug.

Cited by 9 publications

References 0 publications

Everted gut sac model as a tool in pharmaceutical research: limitations and applications

Everted gut sac model as a tool in pharmaceutical research: limitations and applications

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

Síntese e atividade antimicobacteriana de ésteres do ácido pirazinóico e quinolonas

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