Pharmacokinetic Interaction Between High-Dose Methotrexate and Amoxycillin

Ronchera, C.L.; Hernández, Tzasná; Peris, José-Esteban; Torres, Fernando; Granero, Luis; Jiménez, N. V.; Plá, J M

doi:10.1097/00007691-199310000-00004

Cited by 75 publications

(36 citation statements)

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“…31) Amoxicillin decreases the renal clearance of methotrexate, probably due to a competition at the common tubular secretion system. 32) However, the renal excretion of sodium diclofenac is negligible. 8) Thus, an increase in the amoxicillin renal clearance caused by diclofenac could be improbable.…”

Section: )mentioning

confidence: 99%

Effect of Sodium Diclofenac on Serum and Tissue Concentration of Amoxicillin and on Staphylococcal Infection

Groppo

Simões

Ramacciato

et al. 2004

Biological & Pharmaceutical Bulletin

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Amoxicillin is a widely prescribed aminopenicillin, primarily for oral use.1) Ninety percent of the administered dose is absorbed without molecular modifications.2) It provides human serum concentration ranging from 7.6 mg/ml to 10.8 mg/ml when 500 mg/p.o. is used 3,4) ; 15.1 mg/ml when 15.4 mg/kg/p.o. is used, 1) and 14.5 mg/ml when 40 mg/kg/p.o. is used.5) The serum concentrations in rats were 28 mg/ml and 13 mg/ml when amoxicillin doses of 40 mg/kg/p.o. and 7.0 mg/kg/p.o. were administered, respectively. 6,7)

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Section: )mentioning

confidence: 99%

Effect of Sodium Diclofenac on Serum and Tissue Concentration of Amoxicillin and on Staphylococcal Infection

Groppo

Simões

Ramacciato

et al. 2004

Biological & Pharmaceutical Bulletin

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“…MTX inhibits dihydrofolate reductase and is used widely for cancer chemotherapy (Frei et al, 1975;Jackson, 1984). Combined administration of MTX with other drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs) (Ellison and Servi, 1985;Maiche, 1986;Thyss et al, 1986;Ng et al, 1987;Tracy et al, 1992), penicillin antibiotics (Ronchera et al, 1993;Yamamoto et al, 1997;Titier et al, 2002), probenecid (Aherne et al, 1978), and ciprofloxacin (Dalle et al, 2002) can result in severe and life-threatening drug interactions. Of the drugs affecting the pharmacokinetics of MTX, NSAIDs have been well documented.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Inhibition of Methotrexate Excretion by Glucuronides of Nonsteroidal Anti-inflammatory Drugs via Multidrug Resistance Proteins 2 and 4

Kawase

Yamamoto

Egashira

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Combined administration of methotrexate (MTX) and nonsteroidal anti-inflammatory drugs (NSAIDs) can result in a decreased systemic clearance of MTX. To date, inhibition of renal uptake via organic anion transporters and efflux via multidrug resistance-associated protein (MRPs) by NSAIDs has been recognized as possible sites of drug interaction between MTX and NSAIDs. Although most NSAIDs are glucuronidated in kidney tissue and excreted mainly as glucuronide conjugates, it is not fully known whether the glucuronides of NSAIDs (NSAIDs-Glu) inhibit MTX excretion via MRP2 and MRP4. The purpose of this study was to investigate the inhibitory effects of the glucuronides of several NSAIDs (diclofenac, R-and S-ibuprofen, R-and S-flurbiprofen, and R-and S-naproxen), as well as the parent NSAIDs on MTX uptake using human MRP2-and MRP4-expressing inside-out vesicles. Results confirm that all NSAIDs and NSAIDs-Glu examined exhibited stereoselective and concentrationdependent inhibitory effects on MTX uptake via MRP2 and MRP4. Notably, NSAIDs-Glu potently inhibited MTX uptake via MRP2 and MRP4 compared with the corresponding parent NSAIDs except for naproxen in MRP2 and S-flurbiprofen in MRP4. The present results support that the glucuronides of NSAIDs, as well as the parent NSAIDs, are involved in the inhibition of urinary excretion of MTX via MRP2 and MRP4.

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“…Several drugs such as nonsteroidal anti-inflammatory drugs [4], probenecid [5] or penicillin [6,7] are known to reduce methotrexate renal elimination. In cancer patients, drug interactions have also been reported between methotrexate, or its main metabolite 7-hydroxymethotrexate, and benzimidazoles (omeprazole and pantoprazole), resulting in clinically relevant myelosuppression with systemic infections and severe mucositis.…”

Section: Introductionmentioning

confidence: 99%

Suspicion of Drug-Drug Interaction between High-Dose Methotrexate and Proton Pump Inhibitors: A Case Report – Should the Practice Be Changed?

Ranchon¹,

Vantard²,

Gouraud

et al. 2011

Chemotherapy

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We report a case of a potential drug-drug interaction in a woman treated by a first injection of high-dose methotrexate for a T-lymphoblastic lymphoma. Valaciclovir, fluoxetine and pantoprazole were given concomitantly. A methotrexate overdosage was shown at 36 h after infusion associated with a severe renal failure. Alkaline hyperhydration, folinic acid and carboxypeptidase G2 were given. Prescription analyses by pharmacists and literature research have permitted us to suggest that a drug-drug interaction between methotrexate and proton pump inhibitors (PPI) was responsible for this renal failure. Several mechanisms of interaction were suggested and might be related to the inhibition of renal methotrexate transporters by PPI, an increase in the methotrexate efflux to the blood by an upregulation of multidrug resistance protein 3 by PPI or genetic polymorphisms. This case shows that pharmacists can help physicians to optimize patient treatment: they consensually decided on the systematic discontinuation of PPI or a switch to ranitidine when patients were treated by high-dose methotrexate.

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Pharmacokinetic Interaction Between High-Dose Methotrexate and Amoxycillin

Cited by 75 publications

References 0 publications

Effect of Sodium Diclofenac on Serum and Tissue Concentration of Amoxicillin and on Staphylococcal Infection

Effect of Sodium Diclofenac on Serum and Tissue Concentration of Amoxicillin and on Staphylococcal Infection

Stereoselective Inhibition of Methotrexate Excretion by Glucuronides of Nonsteroidal Anti-inflammatory Drugs via Multidrug Resistance Proteins 2 and 4

Suspicion of Drug-Drug Interaction between High-Dose Methotrexate and Proton Pump Inhibitors: A Case Report – Should the Practice Be Changed?

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