Influence of the antibiotics piperacillin, doxycycline, and tobramycin on the pharmacokinetics of methotrexate in rabbits

  title={Influence of the antibiotics piperacillin, doxycycline, and tobramycin on the pharmacokinetics of methotrexate in rabbits},
  author={Heiko Iven and Helmut Brasch},
  journal={Cancer Chemotherapy and Pharmacology},
  • H. Iven, H. Brasch
  • Published 2004
  • Medicine, Biology, Chemistry
  • Cancer Chemotherapy and Pharmacology
SummaryIn rabbits methotrexate (MTX) plasma concentrations showed a triexponential decline after short-term infusion (12 mg/kg in 10 min). Probenecid (50 mg/kg PO 1 h before MTX) and piperacillin (100 mg/kg SC 10 min before MTX plus 50 mg/kg SC 4 h later) increased the plasma concentrations of MTX and its metabolite 7-hydroxy-methotrexate (7-OH-MTX) 40 min to 6 h after the end of MTX infusion. The total body clearance of MTX was reduced, while the elimination half-life and the drug distribution… 

Cephalosporins increase the renal clearance of methotrexate and 7-hydroxymethotrexate in rabbits

The results suggest that cephalosporins are a better choice than penicillin for antibiotic treatment during MTX therapy, because an inhibition of the tubular reabsorption of the cytostatic and its metabolite is best explained.

Pharmacokinetics of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH-MTX) in rats and evidence for the metabolism of MTX to 7-OH-MTX

Differences between the physicochemical properties of MTX and 7-OH-MTX or different affinities for active transport systems may account for the unequal importance of these two excretion pathways for the two compounds.

Enhanced systemic availability of methotrexate in the presence of morin in rats

The present study aimed to investigate the effect of morin on the pharmacokinetics of methotrexate (MTX) in rats. Pharmacokinetic parameters of MTX were determined in rats following an intravenous

Pharmacokinetic interaction between methotrexate and piperacillin/tazobactam resulting in prolonged toxic concentrations of methotrexate.

A 50-year-old female with newly diagnosed Burkitt’s lymphoma who was treated with alternating monthly cycles of IVAC and CODOX-M and piperacillin/tazobactam was initiated as empirical therapy, finding no evidence is available regarding its potential ability to impair methotrexate elimination.

Inhibition of flucloxacillin tubular renal secretion by piperacillin.

Piperacillin inhibits renal and nonrenal elimination of flucloxacillin and might be useful to improve the effectiveness of antibacterial treatment.

Significant interaction between high-dose methotrexate and high-dose piperacillin-tazobactam causing reversible neurotoxicity and renal failure in an osteosarcoma patient

Severe MTX-related toxicity, caused by drug-drug interaction, suggests that the concomitant use of high-dose MTX and high- dose piperacillin-tazobactam should be avoided generally.

Effects of piperacillin/tazobactam or cefepime on folinate dose in patients receiving high-dose methotrexate: A retrospective cohort study using Japanese administrative claims data

  • S. KadomuraS. Imai Y. Takekuma
  • Medicine
    Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners
  • 2021
It was revealed that PIPC/TAZ did not necessarily cause a delay inMTX clearance during HD-MTX therapy, and the co-administration of CFPM with HD- MTX did not affect MTX clearance.

Altered intravenous pharmacokinetics of topotecan in rats with acute renal failure (ARF) induced by uranyl nitrate: Do adenosine A1 antagonists (selective/non-selective) normalize the altered topotecan kinetics in ARF?

The pharmacokinetic disposition of TPT improved considerably upon treatment with DPPX, a selective adenosine A1 antagonist, and may be involved in the tubular secretory pathway when a passive glomerular filtration pathway for elimination was not possible.

β-lactam antibiotics

This chapter describes the drug–drug interactions of the β-lactam antibiotics: penicillins, cephalosporins, carbapenems, and monobactams.



Pharmacokinetics of methotrexate and 7-hydroxymethotrexate following infusions of high-dose methotrexate.

The pharmacokinetics of methotrexate and 7-OH-MTX was influenced by orally coadministered activated charcoal, presumably by inhibition of enteral reabsorption of MTX and 6-hydroxymethotrexate.

Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate in rabbits

From the combined pharmacokinetic data a linear model was constructed for the calculation of 7-OH-MTX plasma concentrations after short-term MTX infusion and for the first 4 h after MTX application the predicted values were in good accordance with the 7- OH-MTZ plasma concentrations actually measured.

Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate in rabbits after intravenous administration

The pharmacokinetics of methotrexate and 7-hydroxy-methotrexate, a major metabolite, were investigated in rabbits after intravenous bolus injection and infusion using a specific HPLC assay and revealed that this metabolite had a longer residence time and a larger Vss as compared with MTX, which were in accordance with its physicochemical properties.

Clearance studies of methotrexate and 7-hydroxy-methotrexate in rabbits after multiple-dose infusion

Saturable renal tubular secretion appeared operative for both drug and metabolite since their renal clearance (based on the free drug to inulin clearance ratios were much greater than unity and the ratios were markedly reduced in 2 rabbits after probenecid treatment.

Effect of penicillin on the renal tubular secretion of methotrexate in the monkey.

It was concluded that MTX and Penicillin share a common secretory system in the kidney and that penicillin blocks MTX secretion by inhibiting cellular uptake and stimulating efflux.

Prolongation and enhancement of serum methotrexate concentrations by probenecid.

Probenecid given at the same time as the bolus injection delayed the disappearance of MTX from the serum and resulted in enhanced concentrations throughout the 24 hours studied.

Inhibition of renal tubular transport of methotrexate by probenecid.

Under steady-state conditions of varied plasma levels of methotrexate (MTX), it was determined that MTX was excreted by renal tubular transport as well as by glomerular filtration.

Pharmacokinetics and organ distribution of methotrexate in the rat.

After intravenous injection of 31 mg/kg methotrexate (MTX), its concentrations were determined in plasma, liver, kidney, bone marrow, stomach, duodenum, jejunum, colon and muscle up to 23 days, using

Toxic reaction to methotrexate in a patient receiving penicillin and furosemide: a possible interaction.

It is believed that a severe toxic reaction to methotrexate developed after furosemide and penicillin V potassium were added, complicated by staphylococcal sepsis, may have resulted from the inhibition of metotrexate renal secretion by furoSemide andpenicillin.

Analysis of methotrexate and 7-hydroxymethotrexate by high-pressure liquid chromatography.

A high-pressure liquid chromatographic method, which utilizes ion-pairing on a mu-Bondapak C18 column, has been developed and provides an efficient and highly sensitive method for detecting impurities in commercially available MTX.