Approach to reduce the non-specific binding in microdialysis

Nirogi, Ramakrishna; Kandikere, Vishwottam; Bhyrapuneni, Gopinadh; Benade, Vijay; Saralaya, Ramanatha; Irappanavar, Shantaveer; Muddana, Nageswararao; Ajjala, Devender Reddy

doi:10.1016/j.jneumeth.2012.06.010

Cited by 25 publications

(16 citation statements)

References 22 publications

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“…Non-specific binding of drug to MD membrane and tubings might be a major concern and should be investigated in vitro prior to in vivo studies [18,19]. Danofloxacin and CP-71,755-27 showed characteristics of non-specific binding that was eliminated by saturating the equipment with the drugs themselves, as previously described [20].…”

Section: Methodsmentioning

confidence: 81%

Microdialysis as a Tool for Drug Quantification in the Bronchioles of Anaesthetized Pigs

Rottbøll

Friis

2013

Basic Clin Pharma Tox

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Target site drug determinations are crucial for optimizing treatment of infectious diseases. There is limited knowledge of antibiotic drug penetration into the pulmonary epithelial lining fluid (PELF) and a lack of easily performed methods for continuous drug sampling hereof. The aim of this study was to develop a readily accessible microdialysis (MD) method for antibiotic drug quantification in PELF of pigs. The fluoroquinolone danofloxacin was administered to anaesthetized pigs allocated to three groups: intravenous injection, intravenous infusion and intramuscular injection. MD probes were guided through a tracheostomy into the distal bronchioles using an insertion tube. Intravenously administered inulin served as a marker of extracellular fluid contamination of PELF. Concentrations of free drug in MD fractions were compared to total and non-protein-bound drug concentrations in plasma. Rising and declining danofloxacin plasma concentrations were rapidly reflected in PELF, suggesting an efficient drug transport across the blood bronchial barrier. The AUC FREE DRUG PELF /AUC FREE DRUG PLASMA ratio was 1.8 (S.D. 0.4, 95% CL 1.4-2.3). Although the probes were placed without fiberscopic or other special equipment, the danofloxacin concentrations in PELF were consistent within the different administration groups. The described MD method for drug quantification in PELF is easily accessible and provides repeatable results. However, trace amount of inulin was detected in the MD fractions, suggesting a local tissue reaction induced by the MD membrane. The significance of this finding needs to be clarified in future studies.

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Section: Methodsmentioning

confidence: 81%

Microdialysis as a Tool for Drug Quantification in the Bronchioles of Anaesthetized Pigs

Rottbøll

Friis

2013

Basic Clin Pharma Tox

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“…In vitro experiments were performed to predict nonspecific binding and described approaches to reduce the degree of adsorption based on a previous study [52]. Firstly, the nonspecific binding to the tubing was assessed by comparing the FLZ concentrations before and after passing through the tubing.…”

Section: Methodsmentioning

confidence: 99%

AnIn VivoMicrodialysis Study of FLZ Penetration through the Blood-Brain Barrier in Normal and 6-Hydroxydopamine Induced Parkinson’s Disease Model Rats

Hou

Liu

et al. 2014

BioMed Research International

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FLZ (N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide) is a novel synthetic squamosamide derivative and a potential anti-Parkinson's disease (PD) agent. The objective of the present study was to investigate the penetration of free FLZ across the BBB and the effects of P-gp inhibition on FLZ transport in normal and 6-hydroxydopamine (6-OHDA) induced PD model rats. In vivo microdialysis was used to collect FLZ containing brain and blood dialysates following intravenous (i.v.) drug administration either with or without pretreatment with the specific P-gp inhibitor, zosuquidar trihydrochloride (zosuquidar·3HCl). A sensitive, rapid, and reliable ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique was developed and validated to quantitate free FLZ levels in the dialysates. No significant differences were observed in the brain/blood FLZ area under the concentration-time curve (AUC) ratio between normal and PD model rats. However, pretreatment with zosuquidar·3HCl markedly increased the AUC ratio in both rat models. In addition, FLZ penetration was similar in zosuquidar·3HCl-pretreated normal and PD rats. These results suggest that P-gp inhibition increases BBB permeability to FLZ, thereby supporting the hypothesis that P-gp normally restricts FLZ transfer to the brain. These findings could provide reference data for future clinical trials and may aid investigation of the BBB permeability of other CNS-active substances.

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“…If the measures of adding albumin or changing tubing material do not solve the problem, it is recommended not to perform microdialysis. More detailed recommendation on how to address the problem with adsorption can be found in the AAPS-FDA workshop white paper (16), as well as in (18,24,57,58). However, in the paper by Nirogi et al, a 60-min pre-equilibration was used, which may hide possible adsorption (58).…”

Section: In Vitro Preparations and Adsorption To Tubings And Probementioning

confidence: 99%

Microdialysis as an Important Technique in Systems Pharmacology—a Historical and Methodological Review

Hammarlund‐Udenaes

2017

AAPS J

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Abstract.Microdialysis has contributed with very important knowledge to the understanding of target-specific concentrations and their relationship to pharmacodynamic effects from a systems pharmacology perspective, aiding in the global understanding of drug effects. This review focuses on the historical development of microdialysis as a method to quantify the pharmacologically very important unbound tissue concentrations and of recent findings relating to modeling microdialysis data to extrapolate from rodents to humans, understanding distribution of drugs in different tissues and disease conditions. Quantitative microdialysis developed very rapidly during the early 1990s. Method development was in focus in the early years including development of quantitative microdialysis, to be able to estimate true extracellular concentrations. Microdialysis has significantly contributed to the understanding of active transport at the blood-brain barrier and in other organs. Examples are presented where microdialysis together with modeling has increased the knowledge on tissue distribution between species, in overweight patients and in tumors, and in metabolite contribution to drug effects. More integrated metabolomic studies are still sparse within the microdialysis field, although a great potential for tissue and disease-specific measurements is evident.

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Approach to reduce the non-specific binding in microdialysis

Cited by 25 publications

References 22 publications

Microdialysis as a Tool for Drug Quantification in the Bronchioles of Anaesthetized Pigs

Microdialysis as a Tool for Drug Quantification in the Bronchioles of Anaesthetized Pigs

AnIn VivoMicrodialysis Study of FLZ Penetration through the Blood-Brain Barrier in Normal and 6-Hydroxydopamine Induced Parkinson’s Disease Model Rats

Microdialysis as an Important Technique in Systems Pharmacology—a Historical and Methodological Review

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