Pediatric nephrology (Berlin, Germany) · 2026
Plasma-saliva correlations for total and unbound mycophenolic acid and its glucuronide in children with nephrotic syndrome.
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Babacz Klaudia, Benedyk Anna, Zachwieja Jacek, Ostalska-Nowicka Danuta, Sobiak Joanna
Аннотация
BACKGROUND: For mycophenolic acid (MPA), therapeutic drug monitoring (TDM) is recommended due to its complex pharmacokinetics. A non-invasive TDM approach using saliva is promising due to its simplicity and minimal invasiveness. This study investigated the relationship between MPA and its glucuronide metabolite (MPAG) levels in saliva and plasma in children with nephrotic syndrome (NS).
METHODS: Salivary MPA (sMPA) and MPAG (sMPAG), as well as total MPA (tMPA), total MPAG (tMPAG), and free MPA (fMPA) in plasma were determined for 23 children aged 4-17 years with NS. All children were treated with mycophenolate mofetil twice daily at the same morning and evening doses based on body surface area. Saliva and blood samples were collected before the next dose (Ctrough), and at 1, 2, 3, 4, 6, 9, and 12 h post-dose.
RESULTS: The concentration-time profiles showed a similar course for tMPA, sMPA, and fMPA, with the highest variability observed for sMPA. The mean Ctrough and maximum concentration (Cmax,ss) for sMPA were nearly twice as high as for fMPA; however, the median values were comparable. The sMPA AUC0-12 correlated moderately with both tMPA and fMPA AUC0-12 (r ~0.4-0.5). The sMPA AUC0-12 was twofold higher in children with proteinuria; however, the difference was not significant between children with and without proteinuria. For children without proteinuria, the median sMPA and tMPA AUC0-12 were 0.296 µg∙h/mL and 46.6 µg∙h/mL, respectively.
CONCLUSIONS: Saliva may represent a promising matrix for MPA TDM in children with NS, as sMPA and sMPAG generally reflected plasma levels. However, salivary pharmacokinetics exhibited considerable variability, and Cmax,ss and early post-dose concentrations may be affected by local drug presence or formulation. While this study establishes the biological feasibility of sMPA measurement, the present data do not support defining a therapeutic salivary threshold.
METHODS: Salivary MPA (sMPA) and MPAG (sMPAG), as well as total MPA (tMPA), total MPAG (tMPAG), and free MPA (fMPA) in plasma were determined for 23 children aged 4-17 years with NS. All children were treated with mycophenolate mofetil twice daily at the same morning and evening doses based on body surface area. Saliva and blood samples were collected before the next dose (Ctrough), and at 1, 2, 3, 4, 6, 9, and 12 h post-dose.
RESULTS: The concentration-time profiles showed a similar course for tMPA, sMPA, and fMPA, with the highest variability observed for sMPA. The mean Ctrough and maximum concentration (Cmax,ss) for sMPA were nearly twice as high as for fMPA; however, the median values were comparable. The sMPA AUC0-12 correlated moderately with both tMPA and fMPA AUC0-12 (r ~0.4-0.5). The sMPA AUC0-12 was twofold higher in children with proteinuria; however, the difference was not significant between children with and without proteinuria. For children without proteinuria, the median sMPA and tMPA AUC0-12 were 0.296 µg∙h/mL and 46.6 µg∙h/mL, respectively.
CONCLUSIONS: Saliva may represent a promising matrix for MPA TDM in children with NS, as sMPA and sMPAG generally reflected plasma levels. However, salivary pharmacokinetics exhibited considerable variability, and Cmax,ss and early post-dose concentrations may be affected by local drug presence or formulation. While this study establishes the biological feasibility of sMPA measurement, the present data do not support defining a therapeutic salivary threshold.