Analyses of AUC<sub>(0–12)</sub> and C<sub>0</sub> Compliances within Therapeutic Ranges in Kidney Recipients Receiving Cyclosporine or Tacrolimus
The AUC (area under the concentration time curve) is considered the pharmacokinetic exposure parameter best associated with clinical effects. Unfortunately, no prospective studies of clinical outcomes have been conducted in adult transplant recipients to investigate properly the potential benefits o...
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MDPI AG
2020-12-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/9/12/3903 |
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| author | Aurelija Radzevičienė Pierre Marquet Rima Maslauskienė Rūta Vaičiūnienė Edmundas Kaduševičius Edgaras Stankevičius |
| author_facet | Aurelija Radzevičienė Pierre Marquet Rima Maslauskienė Rūta Vaičiūnienė Edmundas Kaduševičius Edgaras Stankevičius |
| author_sort | Aurelija Radzevičienė |
| collection | DOAJ |
| description | The AUC (area under the concentration time curve) is considered the pharmacokinetic exposure parameter best associated with clinical effects. Unfortunately, no prospective studies of clinical outcomes have been conducted in adult transplant recipients to investigate properly the potential benefits of AUC<sub>(0–12)</sub> monitoring compared to the C<sub>0</sub>-guided therapy. The aim of the present study was to compare two methods, C<sub>0</sub> (through level) and AUC<sub>(0–12)</sub> (area under the concentration time curve), for assessing cyclosporine and tacrolimus concentrations. The study included 340 kidney recipients. The AUC<sub>(0–12)</sub> was estimated using a Bayesian estimator and a three-point limited sampling strategy. Therapeutic drug monitoring of tacrolimus performed by using AUC<sub>(0–12)</sub> and C<sub>0</sub> showed that tacrolimus in most cases is overdosed when considering C<sub>0</sub>, while determination of the AUC<sub>(0–12)</sub> showed that tacrolimus is effectively dosed for 27.8–40.0% of patients receiving only tacrolimus and for 25.0–31.9% of patients receiving tacrolimus with MMF (mycophenolate mofetil). In the 1–5 years post-transplantation group, 10% higher CsA (cyclosporine) dose was observed, which was proportionate with a 10% higher AUC<sub>(0–12)</sub> exposure value. This indicates good compatibility of the dosage and the AUC(0–12) method. The Bland–Altman plot demonstrated that C<sub>0</sub> and AUC<sub>(0–12)</sub> might be interchangeable methods, while the ROC (receiver operating characteristic) curve analysis of the C<sub>0</sub>/AUC<sub>(0–12)</sub> ratio in the tacrolimus-receiving patient group demonstrated reliable performance to predict IFTA (interstitial fibrosis and tubular atrophy) after kidney transplantation, with an ROC curve of 0.660 (95% confidence interval (CI): 0.576–0.736), <i>p</i> < 0.01. Moreover, AUC<sub>(0–12)</sub> and C<sub>0</sub> of tacrolimus depend on concomitant medication and adjustment of the therapeutic range for AUC<sub>(0–12)</sub> might influence the results. |
| first_indexed | 2024-03-10T14:24:51Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T14:24:51Z |
| publishDate | 2020-12-01 |
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| spelling | doaj.art-f8f6ab4b754447388d5a3efe20f482b02023-11-20T23:07:31ZengMDPI AGJournal of Clinical Medicine2077-03832020-12-01912390310.3390/jcm9123903Analyses of AUC<sub>(0–12)</sub> and C<sub>0</sub> Compliances within Therapeutic Ranges in Kidney Recipients Receiving Cyclosporine or TacrolimusAurelija Radzevičienė0Pierre Marquet1Rima Maslauskienė2Rūta Vaičiūnienė3Edmundas Kaduševičius4Edgaras Stankevičius5Institute of Physiology and Pharmacology, Medical Academy, Lithuanian University of Health Sciences, 9 A. Mickevičiaus Street, LT-44307 Kaunas, LithuaniaINSERM UMR 850, 87025 Limoges, FranceDepartment of Nephrology, Medical Academy, Lithuanian University of Health Sciences, 9 A. Mickevičiaus Street, LT-44307 Kaunas, LithuaniaDepartment of Nephrology, Medical Academy, Lithuanian University of Health Sciences, 9 A. Mickevičiaus Street, LT-44307 Kaunas, LithuaniaInstitute of Physiology and Pharmacology, Medical Academy, Lithuanian University of Health Sciences, 9 A. Mickevičiaus Street, LT-44307 Kaunas, LithuaniaInstitute of Physiology and Pharmacology, Medical Academy, Lithuanian University of Health Sciences, 9 A. Mickevičiaus Street, LT-44307 Kaunas, LithuaniaThe AUC (area under the concentration time curve) is considered the pharmacokinetic exposure parameter best associated with clinical effects. Unfortunately, no prospective studies of clinical outcomes have been conducted in adult transplant recipients to investigate properly the potential benefits of AUC<sub>(0–12)</sub> monitoring compared to the C<sub>0</sub>-guided therapy. The aim of the present study was to compare two methods, C<sub>0</sub> (through level) and AUC<sub>(0–12)</sub> (area under the concentration time curve), for assessing cyclosporine and tacrolimus concentrations. The study included 340 kidney recipients. The AUC<sub>(0–12)</sub> was estimated using a Bayesian estimator and a three-point limited sampling strategy. Therapeutic drug monitoring of tacrolimus performed by using AUC<sub>(0–12)</sub> and C<sub>0</sub> showed that tacrolimus in most cases is overdosed when considering C<sub>0</sub>, while determination of the AUC<sub>(0–12)</sub> showed that tacrolimus is effectively dosed for 27.8–40.0% of patients receiving only tacrolimus and for 25.0–31.9% of patients receiving tacrolimus with MMF (mycophenolate mofetil). In the 1–5 years post-transplantation group, 10% higher CsA (cyclosporine) dose was observed, which was proportionate with a 10% higher AUC<sub>(0–12)</sub> exposure value. This indicates good compatibility of the dosage and the AUC(0–12) method. The Bland–Altman plot demonstrated that C<sub>0</sub> and AUC<sub>(0–12)</sub> might be interchangeable methods, while the ROC (receiver operating characteristic) curve analysis of the C<sub>0</sub>/AUC<sub>(0–12)</sub> ratio in the tacrolimus-receiving patient group demonstrated reliable performance to predict IFTA (interstitial fibrosis and tubular atrophy) after kidney transplantation, with an ROC curve of 0.660 (95% confidence interval (CI): 0.576–0.736), <i>p</i> < 0.01. Moreover, AUC<sub>(0–12)</sub> and C<sub>0</sub> of tacrolimus depend on concomitant medication and adjustment of the therapeutic range for AUC<sub>(0–12)</sub> might influence the results.https://www.mdpi.com/2077-0383/9/12/3903immunosuppressionAUCC<sub>0</sub>C<sub>0</sub>/AUC<sub>(0–12)</sub> ratiocyclosporine and tacrolimus |
| spellingShingle | Aurelija Radzevičienė Pierre Marquet Rima Maslauskienė Rūta Vaičiūnienė Edmundas Kaduševičius Edgaras Stankevičius Analyses of AUC<sub>(0–12)</sub> and C<sub>0</sub> Compliances within Therapeutic Ranges in Kidney Recipients Receiving Cyclosporine or Tacrolimus Journal of Clinical Medicine immunosuppression AUC C<sub>0</sub> C<sub>0</sub>/AUC<sub>(0–12)</sub> ratio cyclosporine and tacrolimus |
| title | Analyses of AUC<sub>(0–12)</sub> and C<sub>0</sub> Compliances within Therapeutic Ranges in Kidney Recipients Receiving Cyclosporine or Tacrolimus |
| title_full | Analyses of AUC<sub>(0–12)</sub> and C<sub>0</sub> Compliances within Therapeutic Ranges in Kidney Recipients Receiving Cyclosporine or Tacrolimus |
| title_fullStr | Analyses of AUC<sub>(0–12)</sub> and C<sub>0</sub> Compliances within Therapeutic Ranges in Kidney Recipients Receiving Cyclosporine or Tacrolimus |
| title_full_unstemmed | Analyses of AUC<sub>(0–12)</sub> and C<sub>0</sub> Compliances within Therapeutic Ranges in Kidney Recipients Receiving Cyclosporine or Tacrolimus |
| title_short | Analyses of AUC<sub>(0–12)</sub> and C<sub>0</sub> Compliances within Therapeutic Ranges in Kidney Recipients Receiving Cyclosporine or Tacrolimus |
| title_sort | analyses of auc sub 0 12 sub and c sub 0 sub compliances within therapeutic ranges in kidney recipients receiving cyclosporine or tacrolimus |
| topic | immunosuppression AUC C<sub>0</sub> C<sub>0</sub>/AUC<sub>(0–12)</sub> ratio cyclosporine and tacrolimus |
| url | https://www.mdpi.com/2077-0383/9/12/3903 |
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