Methodological and Clinical Aspects of Cyclosporin Monitoring: Report of the Association of Clinical Biochemists Task Force

Abstract

Additional key phrases: immunosuppressant drugs; analytical methods; transplantationDuring the last decade a growing number of centres have become involved in the measurement of the immunosuppressive agent cyclosporin, When the UK Cyclosporin Quality Assessment Scheme (UKCQAS) was started by two of us (DH and AI) in 1984 there were 14 participants in the UK; now there are over 50. The increasing number of indications for which cyclosporin can be prescribed, together with the proliferation of centres capable of performing organ transplantation, suggests that an even larger number of laboratories are likely to offer this assay as a service in the future. The purpose of this review is to summarize current information relating to cyclosporin monitoring and to give some indication of the clinical problems surrounding the use of the results. It has been written against the background of three consensus documents, based on input from laboratory scientists and clinicians, all of which have arrived at similar concluslons.l ? Since these consensus reports were written there have been some changes with regard to the immunoassays available for cyclosporin measurement and there have been a number of reports documenting the performance of the newest assays.The present authors have all been involved in the measurement of cyclosporin in a variety of clinical settings and intend that this review should allow laboratory workers and clinicians to make an informed choice when deciding which method to use for the measurement of cyclosporin. To this end we have drawn upon recent literature, Correspondence: Dr D W Holt. 420 our own experience in this field, data from the UKCQAS, and we have surveyed current practices in UK laboratories performing the measurement.We have chosen to concentrate on three main areas. First, the pharmacology of the drug, since this is essential to an appreciation of the methodological problems associated with cyclosporin measurement. Secondly, we have produced a detailed review of analytical methods and their relative performance. Thirdly, we present a summary of the clinical factors which influence the interpretation of the results in the diverse clinical settings in which cyclosporin is used, to provide those who are producing the cyclosporin results with some insight into the problems faced by those who have to use the data. CYCLOSPORINSince the cyclic peptide cyclosporin (cyclosporin A, ciclosporin, cyclosporine, Sandimmun@) began to be included in immunosuppressive protocols, it has had a profound effect on clinical transplantation world-wide, not only in terms of improved organ and patient survival but also in improving more positive public attitudes towards transplantation. One major disappointment which emerged with the clinical use of cyclosporin was that therapeutic doses in man caused a number of adverse side-effects, in contrast to many of the animal species studied. These sideeffects included renal and hepatic dysfunction, hypertension, neurotoxicity, lymphoma, abnormal glucose homeostasis, hyp...

Slow progression of joint damage in early rheumatoid arthritis treated with cyclosporin a

“…0 mmoles/liter; 4) CsA trough levels >200 ng/ml, measured on whole blood using the specific monoclonal antibody radioimmunoassay method (30); and/or 5) systolic or diastolic blood pressure to 160 or 95 mm Hg at 2 consecutive visits. A temporary or permanent increase in dosage was allowed in the event of poor treatment efficacy according to the investigator's global evaluation (up to a maximum of 5 mg/kg/ day).…”

Monitoring C2 Level Predicts Exposure in Maintenance Lung Transplant Patients Receiving the Microemulsion Formulation of Cyclosporine (Neoral)

“…7 To meet these challenges, relatively aggressive immunosuppressive regimens are employed in lung transplantation patients compared with renal or liver transplantation. 8 Currently, a triple immunosuppressive regimen, consisting of a calcineurin inhibitor, steroids and mycophenolate mofetil or azathioprine, is standard at most centers. 4 However, efforts continue to identify improved immunosuppressive strategies that reduce the high incidence of rejection after lung transplantation without exposing patients to additional adverse events, particularly infectious complications that occur with a greater frequency in this population than in recipients of any other type of solid organ allograft, 9 and which are a considerable source of morbidity and mortality.…”

Mechanisms of Calcineurin Inhibitor Nephrotoxicity in Chronic Allograft Injury

“…While oral administration is the preferred route of CsA prophylaxis, its absorption may be incomplete, slow and erratic thus suggesting a major drawback of oral formulation. The bioavailability of oral CsA averages about 30% (Holt et al, 1994) and large inter-and intrapatient variations in CsA absorption have been observed partly due to the unpredictable bioavailability of CsA following oral administration. These variations most likely reflect differences in the seperation of CsA from its vehicle in the intestine.…”