A Study of Organic Acid Transporter‐Mediated Pharmacokinetic Interaction Between NXY‐059 and Cefuroxime

  title={A Study of Organic Acid Transporter‐Mediated Pharmacokinetic Interaction Between NXY‐059 and Cefuroxime},
  author={Matts K{\aa}gedal and Dag Nilsson and Gunilla Huledal and Ingalill Reinholdsson and Yi-fang Cheng and Nils {\AA}senblad and David Pekar and Olof Borg{\aa}},
  journal={The Journal of Clinical Pharmacology},
N is a novel, free-radical-trapping neuroprotectant that, until recently, was in clinical development for the treatment of acute ischemic stroke based on effects seen in experimental animal models. NXY-059 is eliminated primarily by renal excretion, and initial studies have shown that approximately 30% is via active tubular secretion. A phase I study has demonstrated that the active tubular secretion of NXY-059 occurs through an organic acid transporter (OAT). The half-life of NXY-059 is… 
7 Citations
Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke
Current knowledge on specific BBB transporters that can be targeted for improvement of ischemic stroke treatment are reviewed and state-of-the-art perspectives on the rationale for considering BBB transport properties during discovery/development of stroke therapeutics are provided.
Renal Drug Transporters and Drug Interactions
An approach based on substrate–inhibitor associations for predicting potential tubular-based DDIs and preventing their adverse consequences is proposed, and a comprehensive list of known drug interactions with renally-expressed transporters is provided.
Organic anion, organic cation and zwitterion transporters of the SLC22 and SLC47 superfamily (OATs, OCTs, OCTNs and MATEs)
There are 23 transporter proteins in the SLC22 family, which are divided into several subgroups including the organic cation transporters (OCTs), the carnitine/organic cation transporters (OCTNs),
Solute Carrier (SLC) Family Transporters
The major families of the SLC transporters that are involved in drug transport are discussed and information on structures, activities, substrates, inhibitors and genetic polymorphisms are provided to provide a more holistic view of these studies.
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Comparison of the rate of drug transport in natural versus artificial membranes shows discrepancies in absolute magnitudes of 100-fold or more, with the carrier-containing cells showing the greater permeability.
An adaptable HPLC method for the analysis of frequently used antibiotics in ocular samples.
A sensitive, high performance liquid chromatographic (HPLC) method for measuring the concentrations of moxifloxacin, gatifloxicin, linezolid, and cefuroxime in the ocular tissue, optimized for each of the agents, and the resulting analytical sensitivity made the method suitable for clinical investigations of the Ocular penetration of these drugs.
Physiologically based pharmacokinetic evaluation of cefuroxime in perioperative antibiotic prophylaxis
A physiologically based pharmacokinetic model is built with the aim of ensuring adequate antibiotic plasma concentrations in a heterogeneous population during surgery to prevent surgical site infections.


Pharmacokinetics of NXY-059, a nitrone-based free radical trapping agent, in healthy young and elderly subjects.
It appears that NXY-059 is well tolerated and has a highly predictable pharmacokinetic profile, and clearance of N XY-059 was significantly correlated to creatinine clearance in the elderly.
Safety, tolerability and pharmacokinetics of escalating doses of NXY-059 in healthy young and elderly subjects*
NXY-059 was well tolerated at all plasma concentrations tested in both the young and elderly subjects, and no safety concerns were raised.
This study was designed to further characterize the active renal excretion of NXY‐059, and probenecid and cimetidine, substrates for renal systems that transport organic acids and bases, were chosen as model inhibitors.
The pharmacokinetics of cefuroxime after intravenous injection
It is concluded that the favourable pharmacokinetics, especially the high concentrations of unbound cefuroxime in the serum, are likely to aid effective therapy of human infection caused by sensitive bacteria.
The renal clearance of cefuroxime and ceftazidime and the effect of probenecid on their tubular excretion.
The results indicate that in the therapeutic plasma concentration range of cefuroxime its renal clearance is not saturated, and probenecid at therapeutic doses will block tubular excretion of cafurxime almost completely.
Modulation of the central nervous effects of levomethadone by genetic polymorphisms potentially affecting its metabolism, distribution, and drug action
The importance of candidate pharmacogenetic modulators of the central nervous effects of levomethadone is judged by both magnitude of the modulatory effect and frequency of the mutation to assess the utility of genotyping for clinical levometrichadone therapy in a random sample of subjects that resembled the clinical setting.
Prediction of creatinine clearance from serum creatinine.
Values for Ccr were predicted by this formula and four other methods and the results compared with the means of two 24-hour Ccr's measured in 236 patients and the correlation coefficient gave a correlation coefficient between predicted and mean measured CCr's of 0.83; on average, the difference predicted and means measured values was no greater than that between paired clearances.
Effects of cimetidine and probenecid on renal clearance of NXY-059, a novel neuroprotectant: a phase I study to determine the transporter responsible for active secretion
  • Clin Pharmacol Ther
  • 2006
Zinacef in drug knowledge and disease information
  • PDR-Physicians' Desk Reference
  • 2006