Limited sampling strategy for cyclosporine (Neoral®) area under the curve monitoring in pediatric kidney transplant recipients

• Published in: Pediatric transplantation Vol. 9; no. 5; pp. 566 - 573
• Main Authors: Strong, Dawn K., Lai, Amanda, Primmett, Dennis, White, Colin T., Lirenman, David S., Carter, James E., Morrison Hurley, R., Virji, Mumtaz, Ensom, Mary H.H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Munksgaard International Publishers 01.10.2005; Blackwell
• Subjects: Adolescent; Area Under Curve; Biological and medical sciences; Blood Specimen Collection; Child; cyclosporine; Cyclosporine - pharmacokinetics; Drug Monitoring - methods; Female; Humans; Immunosuppressive Agents - pharmacokinetics; Kidney Transplantation; limited sampling strategy; Male; Medical sciences; pediatric; pharmacokinetics; renal transplantation; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; Human; cyclosporine; Pediatrics; Calcineurin inhibitor; renal transplantation; Homotransplantation; Kidney; limited sampling strategy; pediatric; Treatment; Urinary system; Surveillance; Surgery; Area under the curve; Graft; Strategy; Ciclosporin; Immunosuppressive agent; Pharmacokinetics; Limited sampling; Child; Monitoring; Kidney transplantation
• ISSN: 1397-3142; 1399-3046
• DOI: 10.1111/j.1399-3046.2005.00339.x

:  Cyclosporine (CSA; Neoral®) is one of the most common immunosuppressants used in pediatric renal transplantation. Research in adult renal transplant recipients has shown that 2‐h post‐dose concentration (C2) monitoring and limited sampling strategies (LSSs) are better at predicting drug exposure and outcome than trough concentrations (C0). While C0 monitoring is the usual practice in pediatric renal transplant patients, area under the curve (AUC) monitoring has been shown to be superior in terms of predictive ability and outcomes. However, AUC monitoring is impractical and inconvenient in a clinic setting because it involves many blood samples. An LSS provides a reliable alternative. The purpose of this study was to prospectively define an LSS (AUC0−12) for CSA monitoring and to test its predictive performance. As well, an LSS (AUC0−4) for CSA was developed and its predictive performance tested. Blood samples for CSA concentrations were collected in 29 stable pediatric renal transplant patients prior to (t = 0) and at 0.5, 1, 2, 4, 6, and 8 h following a steady‐state morning CSA dose. AUC was calculated by the trapezoidal method; LSSs for AUC0−12 and AUC0−4 were determined using multiple regression analysis in 14 patients; and the LSSs’ predictive performance was tested in 15 additional patients. Both LSSs require two blood samples. For the LSS (AUC0−12), blood samples are required immediately before the dose and 2 h post‐dose: AUC0−12 = 12.45 C0 + 2.17 C2 + 723.16 (r2 = 0.909). For the LSS (AUC0−4), blood samples are required at one and 2 h post‐dose, AUC0−4 = 1.17 C1 + 1.85 C2 − 41.00 (r2 = 0.971). The LSSs demonstrated low bias and high precision for both AUC0−12 and AUC0−4. Our two‐concentration LSSs are accurate and precise predictors that are more clinically useful for our patient population than other LSSs that have been developed for pediatric renal transplant patients. Our study template provides a guide for other centers to develop accurate and precise LSSs specific to their own patient population.