title: Monitoring cyclosporin in blood: between-assay differences at trough and 2 hours post-dose (C2).
abstract: With the introduction of a cyclosporin monitoring strategy based on the use of a sample collected 2 hours after dosing (C2) rather than the predose sample (C0), there was concern that the differences in blood cyclosporin results from the various assay systems would result in assay-specific target ranges for C2 monitoring. In addition, it was not known if the different proportion of cyclosporin metabolites in the blood 2 hours after dosing compared with that seen in predose samples would alter the relationship between the various assay methodologies. The aim of this study was to address these issues using blood samples from patients who had undergone kidney and liver transplantation. To do this, paired samples were collected predose and 2 hours after cyclosporin dosing at various periods following transplantation in kidney (88 paired samples) and liver (165 paired samples) transplant recipients. Cyclosporin was measured in these samples using five different immunoassays (radioimmunoassay, two fluorescent polarization immunoassays, and two homogeneous immunoassays) and high-performance liquid chromatography-mass spectrometry. The results of the study showed that when using these immunoassays to measure blood cyclosporin concentrations at C0, the cross-reactivity of the antibodies in the different immunoassay kits resulted in target therapeutic ranges that would need to vary between assays to maintain parity. However, when the same assays were used to measure the blood cyclosporin concentration at C2, the results were congruent, and assay-specific target therapeutic ranges should not be necessary. Thus, when adopting a C2 monitoring strategy, it is possible to use target therapeutic ranges that are independent of the assay system used.
authors.affiliation: Clinical Pharmacology, Barts and The London, London, United Kingdom. A.Johnston@qmul.ac.uk
authors.forename: Atholl
authors.initials: A
authors.lastname: Johnston
authors.forename: Gary
authors.initials: G
authors.lastname: Chusney
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Schütz
authors.forename: Michael
authors.initials: M
authors.lastname: Oellerich
authors.forename: Terry D
authors.initials: TD
authors.lastname: Lee
authors.forename: David W
authors.initials: DW
authors.lastname: Holt
mesh_terms: D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000097:blood* / Q000493:pharmacokinetics; D016903:Drug Monitoring / Q000379:methods; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000097:blood* / Q000493:pharmacokinetics; D016030:Kidney Transplantation; D016031:Liver Transplantation; D013058:Mass Spectrometry; D011786:Quality Control; D011863:Radioimmunoassay; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine