Monitoring of Mycophenolic Acid Predose Concentrations in the Maintenance Phase More Than One Year After Renal Transplantation

Miura, Masatomo; Niioka, Takenori; Kato, Shoutaro; Kagaya, Hideaki; Saito, Mitsuru; Habuchi, Tomonori; Satoh, Shigeru

doi:10.1097/ftd.0b013e3182197e38

Cited by 16 publications

(8 citation statements)

References 36 publications

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“…The association between the trough level of MPA and clinical outcome such as graft rejection is still controversial. Some researches have shown that the trough level of MPA may be correlated to the patient’s outcomes in kidney transplant recipients ( Borrows et al, 2006 ; Miura et al, 2011 ). However, many studies have indicated a poor correlation between single-point concentrations and MPA-AUC 0-12 h ( Barraclough et al, 2012a ; Chaabane et al, 2013 ; Yamaguchi et al, 2013 ; Cai et al, 2015 ; Jia et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Mycophenolate Mofetil and Development of Limited Sampling Strategy in Early Kidney Transplant Recipients

et al. 2018

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The mycophenolate mofetil (MMF) dose management for optimization of post-transplant treatment especially the early postoperative phase has been well recognized. MMF is a pro-drug of mycophenolic acid (MPA) and is widely used in Chinese renal transplant patients. Until now, the pharmacokinetic (PK) characteristics and model for the area under the concentration–time curve for the 12-h (h) of exposure (AUC0-12 h) of MPA (MPA-AUC0-12 h) estimation were lacking for the new formulation of MMF dispersible tablet in renal transplant patients. The aims of the study were to investigate the PK characteristics of MMF dispersible tablet by detecting the active metabolite of MPA and to establish an accuracy and precision equation for calculating MPA-AUC0-12 h by limited sampling strategy (LSS) in Chinese kidney transplant patients. A total of 60 postoperative kidney transplant recipients were given a multiple-dose of MMF dispersible tablet twice daily combination with tacrolimus (Tac) and steroids. On the 5th day post-transplantation, blood specimens were collected before drug administration and up to 12 h after MMF dispersible tablet administration. Non-compartmental PK analysis was used to determine the data obtained from individual patients. Multivariate stepwise regression analysis was used to develop models for predicting MPA-AUC0-12 h. The 3- and 4-point sampling models using 2 h, 4 h, 8 h and 1 h, 2 h, 4 h and 8 h, respectively, allowed accurate estimation of MPA-AUC0-12 h. PK parameters of MMF dispersible tablet were obtained and the 4-point LSS is the best model for accurate and precise estimation of MPA-AUC0-12 h.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Mycophenolate Mofetil and Development of Limited Sampling Strategy in Early Kidney Transplant Recipients

et al. 2018

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“…In the literature, the association between MPA trough level and clinical outcome such as graft rejection is still controversial. Indeed, in kidney transplantation, some retrospective studies have suggested that MPA C 0 levels may be correlated to the clinical efficiency . However, patients in almost all these studies received a therapy including CsA but very rarely Tac.…”

Section: Discussionmentioning

confidence: 99%

“…Although MPA‐AUC full‐time analysis from 0 to 12 hours (AUC 0–12hours ) is considered the gold standard for assessment of overall drug exposure, it requires at least 8–10 plasma samples drawn over a 12‐hour time interval, thus making it costly and rather impractical for everyday clinical application. In addition, a predose concentration (C 0 ) or a trough concentration, often used as a substitute indicator of AUC in TDM, was shown to be weakly correlated to MPA‐AUC 0–12hours . Therefore, the estimation of MPA‐AUC 0–12hours by using a limited sampling strategy (LSS) using a limited number of blood samples has been suggested as a sufficiently precise but still practical method for the prediction of MPA exposure in adult kidney transplant recipients …”

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confidence: 99%

Limited Sampling Strategy of Mycophenolic Acid in Adult Kidney Transplant Recipients: Influence of the Post‐Transplant Period and the Pharmacokinetic Profile

Chaabane

Aouam

Fredj

et al. 2013

The Journal of Clinical Pharma

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We aimed to develop an accurate and convenient LSS for predicting MPA-AUC(0-12 hours) in Tunisian adult kidney transplant recipients whose immunosuppressive regimen consisted of MMF and tacrolimus combination with regards to the post-transplant period and the pharmacokinetic profile. Each pharmacokinetic profile consisted of eight blood samples collected during the 12-hour dosing interval. The AUC(0-12 hours) was calculated according to the linear trapezoidal rule. The MPA concentrations at each sampling time were correlated by a linear regression analysis with the measured AUC(0-12). We analyzed all the developed models for their ability to estimate the MPA-AUC(0-12 hours). The best multilinear regression model for predicting the full MPA-AUC(0-12 hours) was found to be the combination of C1, C4, and C6. All the best correlated models and the most convenient ones were verified to be also applicable before 5 months after transplantation and thereafter. These models were also verified to be applicable for patients having or not the second peak in their pharmacokinetic profiles. For practical reasons we recommend a LSS using C0, C1, and C4 that provides a reasonable MPA-AUC(0-12 hours) estimation.

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“…For therapeutic monitoring of tacrolimus, the tacrolimus trough level was monitored and the dosage was adjusted to maintain a target concentration of 8 to 10 ng/mL during 1 month post-KT, 5 to 8 ng/mL during 1 month to 1 year, and 3 to 7 ng/mL afterward. Patients received either MMF or EC-MPS, and dosages were adjusted to maintain a target MPA trough concentration of 1.5 to 2.5 mg/L during 1 year post-KT [ 13 , 15 ]. Target concentration was lowered after 1 year post-KT to maintain above 1.0 mg/L.…”

Section: Methodsmentioning

confidence: 99%

Clinical Implication of Mycophenolic Acid Trough Concentration Monitoring in Kidney Transplant Patients on a Tacrolimus Triple Maintenance Regimen: A Single-Center Experience

et al. 2017

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BackgroundThis study was designed to analyze the clinical implications of mycophenolic acid trough concentration monitoring.Material/MethodsWe collected data of patients with mycophenolic acid trough concentration monitoring after their first kidney transplant between November 2006 and March 2015 who were prescribed tacrolimus, mycophenolate, and methylprednisolone. Analyses were performed on 3 periods: 1 month, 1 month to 1 year, and after 1 year post-transplantation. To analyze factors related to acute cellular rejection, logistic regression was used for 1 month, while Cox analysis was used during 1 month to 1 year and after 1 year post-transplantation.ResultsIn the 145 patients receiving mycophenolate mofetil, mean tacrolimus trough ≥7.0 ng/mL (OR=0.177, CI=0.060–0.524, p=0.002) and mean mycophenolic acid trough ≥1.7 mg/L (OR=0.190, CI=0.040–0.896, p=0.036) were protective for rejection during 1 month. Mean mycophenolic acid trough ≥1.7 mg/L (HR=0.179, CI=0.040–0.806, p=0.025) and ≥0.7 mg/L (HR=0.142, CI=0.028–0.729, p=0.019) were related to better rejection-free survival during 1 month to 1 year and after 1 year, respectively. In 399 patients receiving enteric-coated mycophenolate sodium, mean tacrolimus trough ≥7.0 ng/mL (OR=0.258, CI=0.131–0.507, p<0.001) and mean mycophenolic acid trough ≥2.1 mg/L (OR=0.507, CI=0.264–0.973, p=0.041) were protective for rejection during 1 month. Mean mycophenolic acid trough ≥1.7 mg/L (HR=0.519, CI=0.289–0.932, p=0.028) and ≥0.7 mg/L (HR=0.208, CI=0.072–0.602, p=0.004) were related to better rejection-free survival during 1 month to 1 year and after 1 year, respectively.ConclusionsMycophenolic acid trough concentration monitoring can be useful in preventing acute cellular rejection in patients receiving tacrolimus, mycophenolate, and methylprednisolone.

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Monitoring of Mycophenolic Acid Predose Concentrations in the Maintenance Phase More Than One Year After Renal Transplantation

Cited by 16 publications

References 36 publications

Pharmacokinetics of Mycophenolate Mofetil and Development of Limited Sampling Strategy in Early Kidney Transplant Recipients

Pharmacokinetics of Mycophenolate Mofetil and Development of Limited Sampling Strategy in Early Kidney Transplant Recipients

Limited Sampling Strategy of Mycophenolic Acid in Adult Kidney Transplant Recipients: Influence of the Post‐Transplant Period and the Pharmacokinetic Profile

Clinical Implication of Mycophenolic Acid Trough Concentration Monitoring in Kidney Transplant Patients on a Tacrolimus Triple Maintenance Regimen: A Single-Center Experience

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