Abbreviated kinetic profiles to estimate exposure to CyA in renal allograft recipients treated with sandimmun-neoral

Serafinowicz, A.; Gaciong, Zbigniew; Majchrzak, Jadwiga; Bączkowska, Teresa; Nowacka, E; Gradowska, L; Rowińskí, W; M, Lao

doi:10.1016/s0041-1345(96)00092-9

Cited by 13 publications

(8 citation statements)

References 5 publications

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“…Indeed, the best correlation in the present study is obtained from C 2 ( r 2 = 0.9322). This is in agreement with a previous observation 20 . However, the optimally therapeutic range of CsA concentrations at C 2 is still not established, leading to limited usefulness of C 2 as the parameter in CsA monitoring.…”

Section: Discussionsupporting

confidence: 92%

Pharmacokinetic studies of cyclosporine in Oriental kidney transplantation patients

Kungsamrith¹,

Eiam‐Ong

Tungsanga

et al. 2001

Nephrology

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SUMMARY: Pharmacokinetic studies were performed in 10 stable kidney transplantation patients who received microemulsion formulation (Neoral®) of cyclosporine A (CsA) twice daily. No agents having pharmacokinetic effects on CsA had been used in these patients. The values of various basic pharmacokinetic parameters were similar to those reported in Western literature. The complete area under the blood concentration–time curve (AUC) of CsA for the duration of 12 h (12‐h AUC) was determined using the linear trapezoidal rule from seven concentrations at 0, 1, 2, 4, 6, 8, and 12 h after CsA administration. The mean values of 12‐h AUC were 4603.63 ± 344.61 ng h/mL. CsA concentrations at 2 h after dosing (not the trough levels) showed the best correlation with the complete AUC (r2 = 0.9322). The abbreviated AUC of CsA was calculated either by stepwise multiple linear regression analysis or by the linear trapezoidal rule from a few sampling time points. Using stepwise multiple linear regression analysis, which was used in calculating abbreviated AUC in all previous studies, the model equation that had the highest correlation and the lowest prediction error with the complete AUC was derived by using CsA concentrations at 2 and 8 h after dosing (12‐h AUC = 4.262C2 + 8.390C8− 669.417; r2 = 0.9808, absolute prediction error = 3.97 ± 0.96). Two model equations derived using the linear trapezoidal rule provided the best correlation with the complete AUC: (1) The two time points selected model equation 12‐h AUC = 4C2 + 5C8; r2 = 0.9780, absolute prediction error = 6.41 ± 1.22). (2) The three time points selected model equation 12‐h AUC = 4C0 + 3C2 + 5C6; r2 = 0.9475, absolute prediction error = 5.00 ± 1.41). When different pharmacokinetic data sets were applied to the model equations derived using regression analysis, the values of coefficients and the constant of the regression equation had changed from the initial equation. Thus, new model equations will emerge every time the new data are applied. In contrast, the values of coefficients in the model equation calculated using trapezoidal rule were unaltered when tested by the new pharmacokinetic data set. Thus, the abbreviated AUC derived using the linear trapezoidal rule would be simpler than and superior to that obtained using stepwise multiple linear regression analysis in prediction of the complete AUC.

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Section: Discussionsupporting

confidence: 92%

Pharmacokinetic studies of cyclosporine in Oriental kidney transplantation patients

Kungsamrith¹,

Eiam‐Ong

Tungsanga

et al. 2001

Nephrology

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“…12,13 Limited sampling strategies that eliminate the need for multiple blood samples have been developed for CsA. 14,15 The goal of the study was to develop a limited sampling strategy to estimate the AUC of tacrolimus in adult renal transplant patients under routine clinical conditions, and to evaluate its predictive performance in an independent patient population.…”

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confidence: 99%

Evaluation of a Limited Sampling Strategy to Estimate Area Under the Curve of Tacrolimus in Adult Renal Transplant Patients

Armendáriz¹,

Pou²,

Cantarell³

et al. 2005

Therapeutic Drug Monitoring

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Limited sampling strategies have been developed to predict full AUCs. The goal of this study was to develop a limited sampling strategy to estimate the AUC of tacrolimus in adult renal transplant patients and to evaluate its predictive performance in an independent patient population. A total of 27 tacrolimus pharmacokinetic profiles were studied. Blood samples were collected before the dose (0) and at 0.5, 1, 2, 4, 6, 8, and 12 hours postdose. The study was divided into 2 phases. In phase 1, the goal was to obtain a sampling strategy from 14 pharmacokinetic profiles. In phase 2, the bias and precision of the model were evaluated in another 13 pharmacokinetic profiles. The best correlation was achieved at 4 hours after dose (r(2) = 0.790). Stepwise multiple regression analysis determined that the abbreviated AUC at 0, 1, and 4 hours could accurately predict total AUC (r(2) = 0.965). The following formula was developed: AUC = 8.90 + 4.0C0h+ 1.77C1h + 5.47C4h. No significant differences were found between calculated and estimated AUC (165.6 +/- 41.1 and 166.7 +/- 43.2 ng.h/mL, respectively). The mean prediction error (MPE), the relative prediction error (PE), and the mean squared error (MSE) were 0.48 ng.h/mL, 0.16%, and 40.0 ng.h/mL, respectively. The limited sampling with use of the 3 levels at 0, 1, and 4 hours postdose provides accurate, reliable determination of tacrolimus AUC in renal transplant patients.

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“…Serafinowicz et al 41,42 suggested an equation containing c 0 , c 1 h , and c 2 h with mean prediction error of less than 8.8%. Gaspari et al proposed a 3-sample estimating equation using c 0 h , c 1 h , and c 3 h with mean prediction error of 0.3%.…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of Limited Sampling Strategies for Estimation of Cyclosporine Area Under the Concentration–Time Curve in Hematopoietic Stem Cell Transplant Patients

Hadjibabaie

Vazirian²,

Iravani³

et al. 2011

Therapeutic Drug Monitoring

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The aim of this study was to develop and validate limited sampling strategies for accurately predicting 12-hour area under the concentration-time curve (AUC(0-12 h)) to provide a practical method for more precise therapeutic drug monitoring of cyclosporine A in stem cell transplant patients. Steady-state cyclosporine blood concentrations were measured within a dosing interval (12 hours post administration) in 35 allogeneic bone marrow transplant patients receiving 238 mg (±117 mg) twice-daily dose of cyclosporine. Limited sampling strategies were developed by multiple linear regression analysis of relationship between cyclosporine A full AUC(0-12 h) values and different combinations of preselected blood concentrations. Validation of the estimating equations was done by a bootstrap-like cross-validation method. Cross-validation results showed that cyclosporine AUC(0-12 h) could be estimated using either 2 or 3 samples within the first 4 hours after drug administration with good accuracy and precision (absolute prediction error of less than 6.2%). The number of estimated area under the drug concentration-time curves within 15% of observed values was greater than 26 (74%) for models used predose concentration with either c(2h) and c(4h) or both. Most of the previously reported single-sample models showed a systematic error in predicting AUC(0-12 h). Although a statistically significant difference in precision of prediction was seen between 3-sample model using c(0), c(2h), and c(4h) and 2-sample models (c(0), c(2h) or c(0), and c(4h)), such a difference (2%) could not be of clinical importance. Other 2-sample estimating equations (models using c(2h) with either c(6h) or c(10h)) with the same degree of precision appear to be less feasible clinically. Cyclosporine AUC(0-12 h) in bone marrow transplant patients could be estimated using 2 or 3 samples within the first 4 hours after drug administration with good accuracy and precision.

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Abbreviated kinetic profiles to estimate exposure to CyA in renal allograft recipients treated with sandimmun-neoral

Cited by 13 publications

References 5 publications

Pharmacokinetic studies of cyclosporine in Oriental kidney transplantation patients

Pharmacokinetic studies of cyclosporine in Oriental kidney transplantation patients

Evaluation of a Limited Sampling Strategy to Estimate Area Under the Curve of Tacrolimus in Adult Renal Transplant Patients

Development and Validation of Limited Sampling Strategies for Estimation of Cyclosporine Area Under the Concentration–Time Curve in Hematopoietic Stem Cell Transplant Patients

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