Elsevier

Transplantation Proceedings

Volume 37, Issue 7, September 2005, Pages 3019-3021
Transplantation Proceedings

Kidney transplantation
Immunosuppressive protocol
The Area Under the Concentration-Time Curve Versus Trough and Peak Blood Level Monitoring in Renal Transplant Recipients on Cyclosporine

https://doi.org/10.1016/j.transproceed.2005.07.061Get rights and content

Abstract

Objective

The area under the concentration-time curve of cyclosporine microemulsion is the best measure of the absorption and beneficial effects in renal transplant recipients. We sought to determine the best method of monitoring cyclosporine levels in these patients.

Methods

Prospective evaluation of peak cyclosporine blood levels and area under the curve monitoring were performed for 1 year in 65 renal transplant recipients (study group). Cyclosporine trough levels and peak cyclosporine blood levels were correlated with the calculated area under the curve. Cyclosporine trough levels were monitored in equal numbers of matched controls.

Results

There were no significant differences in the incidence of acute rejection, cyclosporine nephrotoxicity, proteinuria, serum creatinine levels, or graft and patient outcomes between the groups (P = .1). Peak cyclosporine blood levels guided by calculating the area under the curve were found to be 27% to 32% lower than previously reported. The correlation coefficient was <70% for cyclosporine trough levels (P < .02) and >90% for peak cyclosporine blood levels (P < .001) when related to the calculated area under the curve. The calculated area under the curve was approximately 6000 ng/mL/h following transplantation, gradually decreasing to approximately 3000 ng/mL/h at 1 year. Both appeared to the acceptable therapeutic values.

Conclusion

Calculating the area under the curve using trough and peak blood levels versus using isolated readings for either of these levels alone is the most effective method of monitoring cyclosporine in recipients undergoing renal transplant.

Section snippets

Methods

A prospective study of 65 randomized patients to evaluate C2 and AUC0–4 was conducted for 1 year. C0 and C2 were used to calculate AUC0–4 according to the Keown algorithm. Equal numbers of age, sex, donor type, human leukocyte antigen mismatch, and immunosuppression-matched patients were selected for comparison as the control group (Table 1). In the study group, daily C2 monitoring began on day 3 following transplantation and continued until day 7, at least once weekly during the first month,

Results

In the study group, the mean C2 during the first month was 1200 ng/mL (1205.75 ± 387.75 ng/mL), 950 ng/mL at 3 months (942.2 ± 287.5 ng/mL), 800 ng/mL at 6 months (817.2 ± 279.3 ng/mL), and 550 ng/mL at 12 months (558.5 ± 94.2 ng/mL). The mean calculated AUC0–4 was 6000 ng/mL/h during the first month (6079.5 ± 803 ng/mL/h), 5000 ng/mL/h at 3 months (4916 ± 126.5 ng/mL/h), 4400 ng/mL/h at 6 months (4326.7 ± 1164.4 ng/mL/h), and 3000 ng/mL/h at 12 months (3042.7 ± 959.3 ng/mL/h). C0 was higher in

Discussion

The aim of this investigation was to attain an adequate AUC for comparison with C0 and C2 values during the study period. C2 in this study was less than that noted in other studies by 27% to 32%, particularly when guided by our therapeutically adequate calculated AUC values. The C2 level was 95% more accurate as a single test predictor of CsA exposure when correlated with calculated AUC compared with <70% correlation for C0 with AUC. Further, C0 correlated with AUC was significantly less after

Acknowledgments

We are sincerely grateful to Mrs Mini Abraham for statistical analyses of our data.

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