[Methods of cyclosporine determination in biological media]

Abstract

Cyclosporine is an immunosuppressive medicine widely used in all grafts and organ transplantations. Its pharmacokinetic characteristics, especially its intensive metabolism, result in great variability potential between and within patients justifying blood levels' determination in patients treated with this drug. If the biological medium (whole blood) selection is of the utmost importance regarding the quality of the result and its validity, the accuracy of the result compared to the blood levels of the drug will depend on the selection of the determination technic involved. At present, various analytical methodologics are available: the immunological technics involving radioactive or non-radioactive tracers, and HPLC (High Performance Liquid Chromatography) technic. The latter requires good chromatography experience; it takes more time to be implemented due prior extraction of cyclosporine from the biological media. This extraction can be effected with organic solvents or by column chromatography: these various technics will be discussed and compared. This methodology enables one to determine metabolite concentrations. Regarding immunological technics, multiclonal or monoclonal antibodies are available for technics involving fluorescence polarization. However, for radioactive tracings and enzymic tracers, only one specific antibody is available. It is important to take into account the specificity of these antibodies relative to the various metabolites regarding results interpretation, their crossing rate being altered in accordance with antibodies and related pathologies. The validity of these technics will be discussed in words of accuracy and exactitude. The laboratory arrangement, the feasability and cost of the technic are also factors to be taken into consideration. At present selection tends towards to most specific technics.