Methods of theophylline assay and therapeutic monitoring of this drug.

ABSTRACT

The purpose of this article is to review various analytical methods of monitoring plasma theophylline. This article was investigated by the "Drug Commission" of SFBC (Société Française de Biologie Clinique). The primary objective is to provide the "know-how", particular for this analysis, which allows the choice between various analytical methods available immunochemical or physiochemical ones. The techniques described are not necessarily the best, they are approved and tested methods which are the most frequently used in routine practice. The proposed immunochemical methods are absorption spectroscopy methods: Enzyme ImmunoAssay (EIA), Enzyme Multiplied ImmunoAssay Technique (EMIT); Reflectance spectroscopy method: Apoenzyme Reactivation Immunoassay System (ARIS); Fluorometry spectroscopy method: Substrate Labeled FluoroImmunoAssay (SLFIA); Fluorometry spectroscopy on solid base; Polarization fluorescence spectroscopy ImmunoAssay (FPIA); Turbidimetric measurements Particle Enhanced Turbidimetric Inhibition ImmunoAssay (PETINIA); Nephelometric measurement Nephelometric Inhibition ImmunoAssay (NIIA). And the proposed physicochemical methods are High Performance Liquid Chromatography (HPLC), Gas Chromatography (GC). The second objective is a review of pharmacological properties of theophylline, necessary for a good understanding of therapeutic drug monitoring intestinal resorption, distribution, metabolism and elimination, drug interactions, dose/response relationship, physiopathological variations and proposed "predictive" "theophylline test". The authors conclude that because of the multiplicity of methodologies used in theophylline therapeutic monitoring the choice of one of them is not easy. The best way to compare different techniques available would be the use of a "reference material" for theophylline monitoring and a quality control network between different clinical pharmacological laboratories.