Therapeutic Mycophenolic Acid Monitoring by Means of Limited Sampling Strategy in Orthotopic Heart Transplant Patients

Therapeutic drug monitoring (TDM) is essential to maintain the efficacy of many immunosuppressant drugs while minimizing their toxicity. TDM of mycophenolate mofetil requires area under the curve AUC determinations but appears laborious, costly, and clinically impractical. To overcome these problems, limited sampling strategies (LSS) have been proposed in adult and pediatric renal transplant patients. The purpose of this study was to develop an LSS in heart transplant patients. Forty-four mycophenolic acid (MPA) full AUC0-12h profiles were generated by high-performance liquid chromatography in nine heart transplant patients during the first 12 weeks posttransplant. Each patient received concomitant cyclosporine and prednisone therapy. Multiple stepwise regression analysis was used to define the time points of MPA levels to explain the MPA AUC0-12h. Agreement between abbreviated AUC and the full AUC0-12h was tested by means of a Bland and Altman analysis. The highest coefficient of determination r2 among MPA AUC and single concentrations (r2 = .610) was observed with C2, while C12 provided the lowest one (r2 = .003). Stepwise linear regression showed that the minimal model with the best estimation of MPA AUC0-12h was obtained at timed values of 1.25, 2, and 6 hours. The corresponding estimated model was AUC = 5.568 + 0.902 * C1.25 + 2.022 * C2 + 4.594 * C6 (r2 = .926). Bland and Altman analysis revealed good agreement between predicted AUC and full AUC. A further interesting model equation obtained by four samples was AUC = 3.800 + 1.015 * C1.25 + 1.819 * C2 + 1.566 * C4 + 3.479 * C6 (r2 = .948).