Only Modest Effect of Lipids and Albumin on Apparent Mycophenolic Acid Clearance in Pediatric Transplant Recipients – a Retrospective Cohort Study

2020 ◽  
Vol 3 (4) ◽  
pp. 01-07
Author(s):  
Carmen Cuellar
Keyword(s):  
Cystatin C ◽  
Mycophenolic Acid ◽  
Therapeutic Drug ◽  
Factors Affecting ◽  
Transplant Patients ◽  
Pediatric Renal Transplant ◽  
Apparent Clearance ◽  
The Face ◽  
Trough Concentrations ◽  
Dose Modifications

Background: There is growing evidence for the need of therapeutic drug monitoring (TDM) of the active compound Mycophenolic Acid (MPA) of mycophenolate mofetil therapy for the management of antirejection therapy after pediatric renal transplantation. While there is substantial inter- and intra-patient variability of MPA exposure, the factors affecting its apparent clearance (CL/F) are understudied. The objective of this study was to determine the relationship between MPA CL/F, eGFR, creatinine, Cystatin C, triglycerides, cholesterol and albumin. Material and Methods: We calculated 1004 estimated mass-spectrometry-determined MPA CL/F using trough concentrations from 35 pediatric renal transplant patients. Results: Mean age was 8.7±4.6 years at transplant with a median follow-up of 5.8 years. Each patient had a median of 30 MPA trough concentrations. The median MPA AUC was 53.21 mg*h/L, the median CL/F was 8.66 L/h. Univariate and multivariate analysis revealed significant correlations of CL/F with creatinine, triglycerides, cholesterol and albumin, and very weakly with hemoglobin, whereas cystatin C was unrelated. Especially higher lipid levels and weekly, but significantly, lower albumin augmented CL/F. However, the correlations were not strong enough to predict CL/F. Conclusion: The data presented indicate the necessity for MPA TDM and suggest that dose modifications may apply in the face of low serum albumin and hyperlipidemia.

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.

scholarly journals Optimized Administration of Voriconazole and Therapeutic Drug Monitoring in Children and Adolescents: A Single-Centre Retrospective Experience from China

2021 ◽  
Author(s):  
Yi-Chang Zhao ◽  
Yang Zou ◽  
Dan Tang ◽  
Chen-Lin Xiao ◽  
Yi-Wen Xiao ◽  
...  
Keyword(s):  
Trough Concentration ◽  
Therapeutic Drug ◽  
Demographic Information ◽  
Therapeutic Level ◽  
Multiple Dosing ◽  
Concentration Data ◽  
Factors Affecting ◽  
Dosage Regime ◽  
Trough Concentrations ◽  
Anti Fungal

Abstract Background Voriconazole (VRC) is a triazole anti-fungal agent and a first-line treatment for invasive fungal infection (IFI) generally. The purpose of our study was performed to explore the factors affecting voriconazole trough concentration (Ctrough) and to show VRC dose adjustment experience in children. Methods The demographic information, concentration data, CYP2C19 genotypes and clinical outcomes of eligible children from January 1th, 2016 to December 31th, 2018 were collected. Factors affecting the voriconazole trough concentration were statistically analyzed. Results A total of 145 trough concentrations in 94 patients were included in this study, 54.5% of which achieved the target concentrations; however, 35.9% and 9.6% of which were sub-therapeutic and super-therapeutic post-multiple dosing. For children ≤ 2, 2–6, 6–12, and 12–18 years, the median VRC maintenance doses of 5.7, 6.7, 5.0 and 3.3 mg/kg twice daily respectively had been required in order to achieve therapeutic level (P < 0.001). Co-administration of proton pump inhibitors affected VRC target trough concentration significantly (P = 0.001). Conclusion Younger pediatric patients might need a higher dosage regime to achieve therapeutic trough concentration. In order to ensure the effectiveness and safety of voriconazole in children, early and repeat monitoring of voriconazole is a powerful tool.

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