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Presenter: PILAR, SALVADOR, A CORUÑA, Spain
Authors: SALVADOR P., OUTEDA M., ALONSO A., LOPEZ A., FERNANDEZ C., SILVA P., MARTIN I.
CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY
M. Outeda1, P. Salvador2, A. Alonso3, A. Lopez3, C. Fernandez3, P. Silva1, I. Martin1
1Pharmacy Department, UNIVERSITY HOSPITAL OF A CORUÑA, A CORUÑA/SPAIN, 2Pharmacy Department, A Coruña University Hospital, A CORUÑA/SPAIN, 3Nephrology Department, UNIVERSITY HOSPITAL OF A CORUÑA, A CORUÑA/SPAIN
Body:
Background Tacrolimus has a narrow therapeutic index with a wide inter and intrapatient variation in pharmacokinetics. The gold standard of determining drug exposure is the estimation of the area-under-the-concentration-time-curve (AUC0-12). However, in routine clinical practice, trough concentration (Ctrough) is used to predict this exposure. The aim of this study is 1)to determine the pharmacokinetic variability of Prograf® in the early and in the stable period after transplantation and 2)to assess the correlation between individual concentrations at various times and the AUC0-12 to find the best sampling time to predict the exposure of Prograf® in a Spanish population of renal transplant recipients. Methods Prospective study of patients who underwent a cadaveric renal transplantation at University Hospital of A Coruña (Spain) between July 2009 and January 2010 and with tacrolimus trough levels in the range 5-15 ng/mL. All recipients were Spanish (Caucasian) and received a triple-immunosuppressive-drug regimen, which consisted of tacrolimus, mycophenolate mofetil or enteric-coated mycophenolate sodium, and steroids. The pharmacokinetics of tacrolimus was assessed 15 days and 3 months after the transplantation. All patients received the same tacrolimus dosage for at least 4 days before this study. Blood samples were taken just before and 1, 2, 3, 4, 6 and 8 h after morning oral administration. Tacrolimus concentrations were measured using chemiluminescent immunoassay on ARCHITECT® platform. AUC0-12 was calculated using the linear trapezoidal rule. Statistical analysis was performed using SPSS version 17.0. Associations between each sample time-point of concentrations and AUC0-12 were evaluated by correlation of determination (r2). The research protocol was approved by the local Ethics Committee and is part of a research project authorized by Carlos III Institute of Health (Ministry of Science and Innovation). Results Twenty renal transplant patients with a mean age of 54.2 ± 12.3 years and a mean body weight of 73.8 ± 16.2 kg were included in the study. The pharmacokinetic parameters are shown in table below.
Early period | Stable period | |||
Mean ± SD | AUC0-12/C (r2) | Mean ± SD | AUC0-12/C (r2) | |
Dose/day/body weight (mg/kg) | 0.09 ± 0.04 | 0.06 ± 0.05 | ||
Ctrough (ng/mL) | 10.3 ± 3.3 | 0.438 | 12.3 ± 2.0 | 0.509 |
C1 (ng/mL) | 19.0 ± 9.4 | 0.199 | 17.3 ± 5.8 | 0.833 |
C2 (ng/mL) | 18.1 ± 6.7 | 0.344 | 20.3 ± 7.1 | 0.948 |
C3 (ng/mL) | 15.5 ± 6.1 | 0.497 | 18.0 ± 5.1 | 0.913 |
C4 (ng/mL) | 15.6 ± 6.7 | 0.471 | 16.1 ± 3.1 | 0.902 |
AUC0-4 (ng.h/mL) | 59.7 ± 15.7 | 0.501 | 69.4 ± 19.9 | 0.972 |
AUC0-12 (ng.h/mL) | 163.6 ± 49.2 | 180.2 ± 31.1 |
Disclosure: All authors have declared no conflicts of interest.
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