Human Microdialysis

Author(s): M. Stahl, R. Bouw, A. Jackson, V. Pay

Journal Name: Current Pharmaceutical Biotechnology

Volume 3 , Issue 2 , 2002

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Microdialysis has been used extensively in animal studies for decades and in human pharmacokinetic studies for about 10 years. Microdialysis samples from the interstitial space which is a defined, anatomical compartment there is no net loss of body fluid the sample is “purified” and no enzymatic degradation takes place because proteins do not pass through the probe membrane into the dialysate microdialysis data relate to the intact molecule time resolution is high compared to biopsy and skin blister techniques radioabelling or induction of a magnetic response is not needed microdialysis is also an alternative method to determine protein binding of a compound in vivo microdialysis can readily be set up in clinical research units without expensive infrastructure. Microdialysis has been used to measure tissue concentrations of endogenous compounds and to investigate the tissue penetration of drugs in a variety of tissues in humans in vivo in both healthy volunteers and patients. Microdialysis data have also been used in PK-PD modelling and to obtain concentration-response relationships locally in tissues in vivo. There are also studies combining microdialysis with imaging techniques, e.g. PET. Microdialysis data may be used in early studies to select the appropriate compound, to optimise dosing regimens and to investigate the kinetic and dynamic consequences in the tissues of drug-drug and drug-disease interactions. Microdialysis can also be used in late phase studies to provide tissue concentration data in support of therapeutic efficacy trials or to create a niche for an already marketed drug. FDA and CPMP documents emphasise the value and importance of human tissue drug concentration data and support the use of microdialysis in humans to obtain such information. Microdialysis can satisfy regulatory requirements by providing data on drug concentrations in a well-defined anatomical tissue compartment at or close to the effect target site. Microdialysis is a versatile technique because of its multifaceted utility, low cost, ease of use, adaptability to different types of compounds and its feasibility for a number of organs and tissues. Equipment and probes for use in various organs have been commercially available for years.

Keywords: microdialysis, nnf, no net flux, cout-cin, dnnf

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Article Details

Year: 2002
Page: [165 - 178]
Pages: 14
DOI: 10.2174/1389201023378373
Price: $65

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PDF: 11