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J T Marsden

Publications and source records attributed to J T Marsden.

17 recordsLinked to original sources

The continuing need for quality assessment of cyclosporine measurement.

The returns from the United Kingdom Cyclosporin Quality Assessment Scheme were analyzed for the period June 1987 to August 1988. During this time the number of laboratories in the Scheme increased from 102 to 124 and the proportion of laboratories using nonspecific assay methods declined, as did the proportion of them measuring cyclosporine in plasma. Seven different methods were used to measure the drug in blood, and the seven methods gave seven different results when used to measure patients' samples. The results, from lowest to highest, differed by a factor of approximately 3.4. The within-assay coefficient of variation (CV) was acceptable for all methods, but the between-assay and between-center CVs were poor. HPLC gave higher CVs than did the immunoassays.

Cyclosporins

The influence of haematocrit on blood cyclosporin measurements in vivo.

The influence of haematocrit on blood cyclosporin measurements has been studied in 276 paired blood and plasma samples from 21 renal transplant patients. A highly significant correlation was found between blood and plasma cyclosporin concentrations, r = 0.8744, but the correlation between blood or plasma cyclosporin and haematocrit was not significant. The ratio of blood/plasma cyclosporin did not significantly increase with increasing haematocrit. It was concluded that in vivo the influence of haematocrit on the measurement of blood cyclosporin concentrations was negligible.

Cyclosporins

Monoclonal antibodies for radioimmunoassay of cyclosporine: a multicenter comparison of their performance with the Sandoz polyclonal radioimmunoassay kit.

The performance of a radioimmunoassay kit containing monoclonal specific and nonspecific antibodies to cyclosporine (Sandimmun-Kit; Sandoz Ltd., Basle, Switzerland) was compared with that of the original Sandoz polyclonal radioimmunoassay kit (Ciclosporin RIA-Kit). A total of 1320 blood and plasma samples from patients receiving cyclosporine after kidney, heart, liver, and bone-marrow transplantation were analyzed at six centers. For blood samples the median result on using the specific assay was about 50% of the polyclonal assay result after kidney and bone-marrow transplantation, about 33% after heart and liver transplantation; comparable figures for plasma samples were 70 and 40%. The monoclonal nonspecific-antibody assay produced results 10% to 140% higher than polyclonal-assay results, depending on sample matrix and transplant indication; the largest difference was seen in samples from heart- and liver-transplant recipients. Evidently the specific-antibody assay provides a convenient alternative to high-performance liquid chromatography for specific measurement of the drug, but the role of the new nonspecific antibody, possessing an even broader spectrum of cross-reactivity with cyclosporine metabolites than the original polyclonal antiserum, has yet to be defined.

Antibodies

Blood cyclosporin concentrations and renal allograft dysfunction.

Forty nine renal allograft recipients taking oral cyclosporin suffered 76 episodes of renal dysfunction within six months of transplantation. These episodes were diagnosed as graft rejection or cyclosporin induced nephrotoxicity on the basis of histological findings in allograft biopsy specimens and the response to treatment. Mean predose blood cyclosporin concentrations measured by radioimmunoassay during the week before the onset of renal dysfunction were significantly higher when the cause was cyclosporin toxicity rather than graft rejection (392 v 741 nmol/l (471 v 891 ng/ml). During this period there was a significant association between both the frequency of measurements above 666 nmol/l (800 ng/ml) and the diagnosis of toxicity and the frequency of measurements below 333 nmol/l (400 ng/ml) and the diagnosis of allograft rejection. Cyclosporin measurements made at the time of biopsy and reference to the highest or lowest concentrations measured during the week preceding biopsy were of less value in distinguishing between the two groups. Despite lacking specificity for the parent compound, the radioimmunoassay used produced results which were of clinical value in optimising cyclosporin treatment.

Adult

The United Kingdom Cyclosporin Quality Assessment Scheme.

Data from a quality assessment scheme designed to test the measurement of cyclosporin are presented. Almost all of the participating 27 centres were using a radioimmunoassay for the measurement and, during the course of 16 months, a number of variables were tested, including accuracy, sensitivity, recovery of added cyclosporin, and within- and between-assay reproducibility. Accuracy of the measurement, judged by the mean results for spiked samples, was good, but values varied widely. Sensitivity tended to be overestimated, with a significant number of false-positive results being reported. The precision profile for the assay showed that there was no intrinsic difference in the precision of measurement using either plasma or whole blood as the sample matrix; but reproducibility for patient samples tended to be better using blood because drug concentrations are higher compared with plasma. We conclude that, whereas the results overall were encouraging, there were wide between-centre variations for the measurement, which could be compounded even further by the use of plasma or serum as the sample matrix.

Cyclosporins

The effect of vehicle on the oral absorption of cyclosporin.

Twelve healthy volunteers received four separate doses of cyclosporin (5 mg kg-1). On three occasions the neat oil suspension (Sandimmun) was given dispersed in a different liquid vehicle and on one occasion the suspension was taken directly. Measurement of whole blood cyclosporin concentrations by radioimmunoassay showed no significant difference in the pharmacokinetic parameters of absorption between the neat preparation and the three dispersants used (milk, milk + chocolate flavouring and orange juice).

Adult