Effects of Antacid on Absorption and Excretion of New Quinolones

Shiba, Kohya; Sakamoto, Mitsuo; Nakazawa, Yasushi; Sakai, Osamu

doi:10.2165/00003495-199500492-00098

Cited by 15 publications

(7 citation statements)

References 3 publications

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“…In this study, the absorption of CPFX was more potently inhibited by AL than that of OFLX (Tables 1 and 2 ). This finding is also consistent with a clinical study showing that the influence of AL on the absorption of NQs varies among NQs and CPFX is more vulnerable to AL than OFLX [ 9 ]. This difference can be also explained by the in vitro binding data.…”

Section: Discussionsupporting

confidence: 92%

Food intake attenuates the drug interaction between new quinolones and aluminum

Imaoka

Abiru

Akiyoshi

et al. 2018

J Pharm Health Care Sci

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BackgroundIntestinal absorption of new quinolones is decreased by oral administration of polyvalent metal cations. Some clinical studies have demonstrated this drug - drug interaction is more prominent under fasted condition. However, the effect of food intake on the extent of drug - drug interaction between new quinolones and metal cations remains to be investigated quantitatively and systematically. The aim of this study was to develop an animal model that enables to evaluate the effect of food intake on the extent of drug - drug interaction in the gastrointestinal tract by chelation and to apply the model to evaluate quantitatively the effect of food intake on the drug - drug interaction between two new quinolones, ofloxacin or ciprofloxacin and sucralfate.MethodsThe rats were orally administered new quinolones (5.3 mg/kg of ofloxacin or 10 mg/kg of ciprofloxacin) with or without 13.3 mg/kg of sucralfate under fasted or fed condition and plasma concentration profiles of new quinolones were monitored. To the fed group, standard breakfast used in human studies was pasted and administered at a dose of 8.8 g/kg.ResultsThe area under the plasma concentration - time curves (AUC0–6) of ofloxacin and ciprofloxacin under the fasted condition were significantly decreased to 28.8 and 17.1% by co-administration of sucralfate, respectively. On the contrary, sucralfate moderately decreased the AUC0–6 of ofloxacin and ciprofloxacin to 54.9 and 33.2%, respectively, under fed condition. The effects of sucralfate and food intake on the kinetics of ofloxacin in this study were well consistent with the results of previous clinical trial.ConclusionsThe developed animal model quantitatively reproduced the effect of food intake on the drug - drug interaction between ofloxacin and sucralfate. The similar influences were observed for the drug - drug interaction between ciprofloxacin and sucralfate, suggesting that the extent of drug - drug interaction caused by chelation is generally attenuated by food intake.

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Section: Discussionsupporting

confidence: 92%

Food intake attenuates the drug interaction between new quinolones and aluminum

Imaoka

Abiru

Akiyoshi

et al. 2018

J Pharm Health Care Sci

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“…The small magnitudes of relative change in both C max (6.1%) and AUC (-15.2%) for rufloxacin indicate overall little sensitivity to bioavailability changes because of aluminum/magnesium interactions [18]. The most common source of aluminum was aluminum hydroxide originating predominantly from the crossover study of Shiba et al, which tested the effects of aluminum hydroxide on FQ bioavailability [71]. N/A: not available; C max : maximum plasma concentration (µg•mL −1 ); AUC: area-under-the-curve of the concentration plasma profile (µg•h•mL −1 ); Calculated k a : calculated absorption rate constant (h −1 ) using Equations ( 1) and ( 2) and the methods outlined in Section 2.1 of this manuscript.…”

Section: Resultsmentioning

confidence: 99%

“…The small magnitudes of relative change in both C max (6.1%) and AUC (–15.2%) for rufloxacin indicate overall little sensitivity to bioavailability changes because of aluminum/magnesium interactions [ 18 ]. The most common source of aluminum was aluminum hydroxide originating predominantly from the crossover study of Shiba et al, which tested the effects of aluminum hydroxide on FQ bioavailability [ 71 ].…”

Section: Resultsmentioning

confidence: 99%

Effects of Magnesium, Calcium, and Aluminum Chelation on Fluoroquinolone Absorption Rate and Bioavailability: A Computational Study

et al. 2021

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Fluoroquinolones (FQs) are a widespread class of broad-spectrum antibiotics prescribed as a first line of defense, and, in some cases, as the only treatment against bacterial infection. However, when administered orally, reduced absorption and bioavailability can occur due to chelation in the gastrointestinal tract (GIT) with multivalent metal cations acquired from diet, coadministered compounds (sucralfate, didanosine), or drug formulation. Predicting the extent to which this interaction reduces in vivo antibiotic absorption and systemic exposure remains desirable yet challenging. In this study, we focus on quinolone interactions with magnesium, calcium and aluminum as found in dietary supplements, antacids (Maalox) orally administered therapies (sucralfate, didanosine). The effect of FQ–metal complexation on absorption rate was investigated through a combined molecular and pharmacokinetic (PK) modeling study. Quantum mechanical calculations elucidated FQ–metal binding energies, which were leveraged to predict the magnitude of reduced bioavailability via a quantitative structure–property relationship (QSPR). This work will help inform clinical FQ formulation design, alert to possible dietary effects, and shed light on drug–drug interactions resulting from coadministration at an earlier stage in the drug development pipeline.

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“…Metal ion-containing drugs that interact with the new fluoroquinolones include aluminumand magnesium-containing antacids, ferrous sulphate and sucralfate, which is a complex of aluminum hydroxide and sulphated sucrose (18). Metal ion-containing drugs have been reported to cause a reduction in fluoroquinolone bioavailability ranging from 19% to 88%, depending on the specific metal ion-containing drug and the specific fluoroquinolone (6,129,(233)(234)(235)(236)(237)(238)(239). Iron has less of an impact than sucralphate and antacids (17,18,233).…”

Section: Metal Ion-containing Drugsmentioning

confidence: 99%

“…ND No data. Adapted from references 6,9,13,129,218,222,[233][234][235][236][237][238][239][240][241][242][243][244][245][246][247][248][249][250][251] thought to be the result of reduced metabolism of phenytoin, caused by fluoroquinolone inhibition of the cytochrome P450 isoenzyme (6). Studies have not yet been conducted to investigate whether any of the new fluoroquinolones also interact with phenytoin.…”

mentioning

confidence: 99%