Population Pharmacokinetics of Cyclosporine in Clinical Renal Transplant Patients

K, Wu; Cui, Yu Xin; Guo, Jipeng; Zhou, Ying; Zhai, Suodi; Cui, Fude; Lu, Wei

doi:10.1124/dmd.105.004358

Cited by 47 publications

(57 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, the final model, a simple E max model with a fixed E 0 (-0.812%), was successfully used to describe rosuvastatin pharmacodynamics. Moreover, the robustness of the final model was evaluated by the nonparametric bootstrap and the datasplitting methods [51,52] , which indicated that selected combinations of data yielded results very similar to those obtained using the original full data set. The predictive performance of the final model was confirmed by the visual predictive check using Monte Carlo simulations, which showed that the mean values of LDL-C reduction (%) from the one-dose trials were mostly distributed within the 5th-to 95th-percentile boundaries of the predictive dose-response profiles for both Westerners and Asians.…”

Section: Discussionmentioning

confidence: 95%

Race differences: modeling the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients

Yang

Wang

et al. 2010

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: To evaluate race differences in the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients using a population pharmacodynamic (PPD) model generated and validated using published clinical efficacy trials. Methods: Published studies randomized trials with rosuvastatin treatment for at least 4 weeks in hypercholesterolemia patients were used for model building and validation. Population pharmacodynamic analyses were performed to describe the dose-response relationship with the mean values of LDL-C reduction (%) from dose-ranging trials using NONMEM software. Baseline LDL-C and race were analyzed as the potential covariates. Model robustness was evaluated using the bootstrap method and the data-splitting method, and Monte Carlo simulation was performed to assess the predictive performance of the PPD model with the mean effects from the onedose trials. Results: Of the 36 eligible trials, 14 dose-ranging trials were used in model development and 22 one-dose trials were used for model prediction. The dose-response of rosuvastatin was successfully described by a simple E max model with a fixed E 0 , which provided a common E max and an approximate twofold difference in ED 50 for Westerners and Asians. The PPD model was demonstrated to be stable and predictive. Conclusion: The race differences in the pharmacodynamics of rosuvastatin are consistent with those observed in the pharmacokinetics of the drug, confirming that there is no significant difference in the exposure-response relationship for LDL-C reduction between Westerners and Asians. The study suggests that for a new compound with a mechanism of action similar to that of rosuvastatin, its efficacy in Western populations plus its pharmacokinetics in bridging studies in Asian populations may be used to support a registration of the new compound in Asian countries.

show abstract

Section: Discussionmentioning

confidence: 95%

Race differences: modeling the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients

Yang

Wang

et al. 2010

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…Han et al [66] reviewed the studies of covariates on pharmacokinetics of cyclosporine, showing a significant decrease in CL/F, Vd/F and absorption rate constant (k a ) [67] of cyclosporine with increasing age [67,68]. However, early pharmacokinetic studies focusing on agedependent influence on cyclosporine disposition have all failed to identify a clinically relevant effect of age on drug exposure [55,69].…”

Section: Cyclosporinementioning

confidence: 98%

Pharmacokinetics and pharmacodynamics of immunosuppressive drugs in elderly kidney transplant recipients

Shi

Hesselink

Gelder

2015

Transplantation Reviews

View full text Add to dashboard Cite

“…Since our methodology is based on simulated data, a published Pop-PK model of cyclosporine (CsA) in clinical renal transplant patients [25] is chosen to illustrate our proposed evaluation procedure of LSS. First, using this model, a full sampling data set will be generated to serve the estimation of AUC ref .…”

Section: Methodsmentioning

confidence: 99%

“…A one-compartment Pop-PK model with first-order elimination and absorption rate for cy-closporine (CsA) is chosen to illustrate our proposed approach [25]. Typical values of model parameters are used in this paper and summarized in Table 1.…”

Section: The Pop-pk Modelmentioning

confidence: 99%

Simulation Based Assessment of Limited Sampling Strategies Reliability in the Estimation of the Area Under the Concentration-Time Curve

Asl¹,

Nekka²,

2015

J In Silico In Vitro Pharmacol

View full text Add to dashboard Cite

The area under the plasma drug concentration-time curve (AUC), representing the total drug exposure over time, is a common pharmacokinetic (PK) surrogate to inform the issue of therapy. Reliability of its estimation highly depends on the frequency of blood sampling. To reduce the cost and inconvenience of blood withdrawal, limited sampling strategies (LSS) have been proposed, with two main approaches for their development and implementation, whether the multiple linear regression-based LSS (R-LSS) or the Bayesian-based LSS (B-LSS). Regardless of the method used, evaluation of the predictive capacity of LSS is critical. Transferring an LSS between different clinical settings is an overlooked aspect, threatening thus the extension of its informed use. In the current paper, we study the reliability of a chosen LSS by proposing a hybrid approach that takes advantage of both R-LSS and B-LSS to analyze its robustness and success rate. The impact of variability on the LSS reliability is also investigated. As a result, we were able to show that our method enhances the selection of the best LSS and informs the associated risk to their transferability. This simulation-based methodology should be added to routine procedures of LSS development to complement traditional validations.

show abstract

Population Pharmacokinetics of Cyclosporine in Clinical Renal Transplant Patients

Cited by 47 publications

References 25 publications

Race differences: modeling the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients

Race differences: modeling the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients

Pharmacokinetics and pharmacodynamics of immunosuppressive drugs in elderly kidney transplant recipients

Simulation Based Assessment of Limited Sampling Strategies Reliability in the Estimation of the Area Under the Concentration-Time Curve

Contact Info

Product

Resources

About