Validated LC–MS/MS method for quantitation of total and free mycophenolic acid concentration and its application to a pharmacokinetic study in pediatric renal transplant recipients

2020 ◽  
Author(s):  
Yan Liu ◽  
Longshan Liu ◽  
Jingjie Li ◽  
Qian Fu ◽  
Huanxi Zhang ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Acid Concentration ◽  
Pharmacokinetic Study ◽  
Mycophenolic Acid ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Pediatric Renal Transplant ◽  
Pediatric Renal Transplant Recipients

scholarly journals The Pharmacokinetic-Pharmacodynamic Relationship for Total and Free Mycophenolic Acid in Pediatric Renal Transplant Recipients: A Report of the German Study Group on Mycophenolate Mofetil Therapy

2002 ◽  
Vol 13 (3) ◽  
pp. 759-768
Author(s):  
Lutz T. Weber ◽  
Maria Shipkova ◽  
Victor W. Armstrong ◽  
Natalie Wagner ◽  
Ekkehard Schütz ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Renal Transplant ◽  
Mycophenolic Acid ◽  
Initial Phase ◽  
Stable Phase ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Characteristic Analysis ◽  
Pediatric Renal Transplant ◽  
Pediatric Renal Transplant Recipients

ABSTRACT. It is currently being debated whether pharmacokinetic monitoring of mycophenolic acid (MPA), the active constituent of mycophenolate mofetil (MMF), can optimize MMF therapy after organ transplantation. This open-label longitudinal study in pediatric renal transplant recipients was designed to investigate the pharmacokinetic (PK)/pharmacodynamic relationship of total and free MPA and to establish PK values for the assessment of an individual’s MPA PK parameters. Fifty-four children, aged 2.2 to 17.8 yr, on an immunosuppressive triple regimen consisting of cyclosporin A, prednisone, and MMF (600 mg/m2 body surface area twice daily) were investigated 1 wk and 3 wk (initial phase) and 3 mo and 6 mo (stable phase) after renal transplantation. MPA was measured by reverse phase HPLC, free MPA by HPLC after separation by ultrafiltration. There was an association between the risk of acute rejection episodes and MPA-AUC0-12 values or MPA predose levels; by receiver operating characteristic analysis, an AUC0-12 of 33.8 mg × h/L in the initial phase posttransplant had a diagnostic sensitivity of 75% and a diagnostic specificity of 64% for discrimination of patients with acute rejections. The respective discrimination threshold for the MPA predose concentration was 1.2 mg/L with a sensitivity of 83% and a specificity of 64%. In contrast, high free, but not total, MPA-AUC0-12 values were associated with an increased risk of the MMF-related side effects leukopenia and/or infections. These data indicate that therapeutic drug monitoring of MPA has the potential for optimization of MMF efficacy in this patient population by steering patients away from the low values of MPA PK variables that are associated with an increased rejection risk. For the assessment of the toxic risk of MMF regarding leukopenia and/or infections, measurement of free MPA appears to be more appropriate.

scholarly journals Comparison of the Emit Immunoassay with HPLC for Therapeutic Drug Monitoring of Mycophenolic Acid in Pediatric Renal-Transplant Recipients on Mycophenolate Mofetil Therapy

2002 ◽  
Vol 48 (3) ◽  
pp. 517-525 ◽  
Author(s):  
Lutz T Weber ◽  
Maria Shipkova ◽  
Victor W Armstrong ◽  
Natalie Wagner ◽  
Ekkehard Schütz ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Renal Transplant ◽  
Acute Rejection ◽  
Mycophenolic Acid ◽  
Therapeutic Drug ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Increased Risk ◽  
Pediatric Renal Transplant ◽  
Pediatric Renal Transplant Recipients

Abstract Background: HPLC is currently the preferred method for accurate measurement of mycophenolic acid (MPA). This study was designed to validate the Emit compared with HPLC in relation to clinical outcome measurements. Methods: Pediatric renal-transplant recipients (n = 50) on an immunosuppressive triple regimen consisting of cyclosporin A, prednisone, and mycophenolate mofetil (600 mg/m2 twice per day) were investigated in an open-label prospective study. Pharmacokinetic profiles over 12 h were obtained at 1 week, 3 weeks, 3 months, and 6 months posttransplant. Plasma MPA was measured by both reversed-phase HPLC and the Emit immunoassay. Results: There was an association between the risk of acute rejection episodes and low area under the curve values from t0 to t12h (AUC0–12) for MPA (MPA-AUC0–12) or predose concentrations of MPA derived from both HPLC and Emit measurements. According to ROC analysis, an AUC value of 33.8 mg · h/L for MPA from t0 to t12h (MPA-AUC0–12) determined by HPLC had a diagnostic sensitivity of 80% and a diagnostic specificity of 57%. The corresponding value of the Emit was 36.1 mg · h/L. For the predose concentration (MPA-c12), a concentration of 1.2 mg/L determined by HPLC and 1.4 mg/L determined by Emit gave a sensitivity of 80% and a specificity of 60%, respectively. There was no association of any pharmacokinetic variables derived from total MPA measurements with an increased risk of side effects related to mycophenolate mofetil. Conclusions: The Emit assay appears to have a comparable diagnostic efficacy to HPLC for assessing the risk of acute rejection in pediatric renal-transplant recipients. However, because of the cross-reactivity of the antibody used in the Emit assay with the active MPA acyl glucuronide metabolite, the decision thresholds for the Emit were higher than those calculated from HPLC measurements.

Monitoring of mycophenolic acid in pediatric renal transplant recipients

2001 ◽  
Vol 33 (1-2) ◽  
pp. 1040-1043 ◽  
Author(s):  
V.W. Armstrong ◽  
M. Shipkova ◽  
E. Schütz ◽  
L. Weber ◽  
B. Tönshoff ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Mycophenolic Acid ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Pediatric Renal Transplant ◽  
Pediatric Renal Transplant Recipients

Long-Term Pharmacokinetics of Mycophenolic Acid in Pediatric Renal Transplant Recipients Over 3 Years Posttransplant

2008 ◽  
Vol 30 (5) ◽  
pp. 570-575 ◽  
Author(s):  
Lutz T Weber ◽  
Britta Hoecker ◽  
Victor W Armstrong ◽  
Michael Oellerich ◽  
Burkhard Tönshoff
Keyword(s):  
Renal Transplant ◽  
Mycophenolic Acid ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Pediatric Renal Transplant ◽  
Pediatric Renal Transplant Recipients
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