Comparison of free plasma versus saliva mycophenolic acid exposure following mycophenolate mofetil administration in adult kidney transplant recipients

Cossart, Amelia R.; Staatz, Christine E.; Gorham, Gillian; Barraclough, Katherine A.

doi:10.1016/j.clinbiochem.2021.11.008

Cited by 3 publications

(11 citation statements)

References 13 publications

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“…Therefore, they suggested that saliva is not reliable marker of C P MPA levels. 12 Our research aimed to make a connection between presence of adverse effects and unbound MPA concentration. In our clinical practice, blood for MPA determination was taken immediately before morning dose (C trough determination) as part of routine practice.…”

Section: Discussionmentioning

confidence: 99%

“…Oppositely, some authors did not demonstrate relationship between C SAL and either total or free C P MPA concentrations. Therefore, they suggested that saliva is not reliable marker of C P MPA levels 12 …”

Section: Discussionmentioning

confidence: 99%

“… 11 It has been shown that plasma MPA exposure, reflected by the area under the concentration‐time curve (AUC), varies widely in patients following the same dosage. 10 , 12 Previous studies reported that the MPA AUC 0‐12 is closely related to the risk for acute rejection. 13 , 14 , 15 Also, results of the previous studies demonstrated association between MPA exposure, ALB and adverse effects.…”

Section: Introductionmentioning

confidence: 99%

“…Also, there is potential of low adherence of intraindividaul variability 11 . It has been shown that plasma MPA exposure, reflected by the area under the concentration‐time curve (AUC), varies widely in patients following the same dosage 10,12 . Previous studies reported that the MPA AUC 0‐12 is closely related to the risk for acute rejection 13–15 .…”

Section: Introductionmentioning

confidence: 99%

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Utility of salivary mycophenolic acid concentration monitoring: Modeling and Monte Carlo validation approach

Catić‐Đorđević

Stefanović

Pavlović

et al. 2022

Pharmacology Res & Perspec

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The results of the previous studies demonstrated an association between mycophenolic acid (MPA) exposure, serum albumin level (ALB), and adverse effects in kidney transplant patients. The aim was the identification of mathematical correlation and association between both, total and unbound MPA concentration in relation to ALB, body mass (BM), age and estimated glomerular filtration rate (eGFR) in stable kidney transplant recipients. Furthermore, investigation was conducted with the aim to clarify the role of salivary concentration (C SAL ) of MPA in adverse effect profile. In order to analyze the association between total and salivary concentration of MPA in relation to ALB, BM, age and eGFR, a least squares method for determining the correlation between these parameters was performed. In addition, derived mathematical model based on experimental data can also be performed and simulated through the Monte Carlo (MC) approach. Adverse effects were grouped according to the nature of symptoms and scored by a previously published validated system. Numerically calculated values of C SAL from the models [C SAL = f (ALB, BM, age, eGFR, C P ) = a 00 + a 10 *(ALB, BM, age, eGFR) + a 01 *C P ] were then compared with those from validation set of patients, where the best fitting model was for ALB [C SAL = 54.96–1.64*ALB +13.4*C P ]. Adverse effects estimation showed the difference in esthetic score, positively correlated with C SAL in the lower ALB group (145.41 ± 219.02 vs. 354.08 ± 262.19; with statistical significance p = .014) and almost significant for gastrointestinal score (167.69 ± 174.79 vs. 347.55 ± 320.95; p = .247). The study showed that C SAL MPA may contribute to management of adverse effects, but these findings require confirmation of clinical utility.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Utility of salivary mycophenolic acid concentration monitoring: Modeling and Monte Carlo validation approach

Catić‐Đorđević

Stefanović

Pavlović

et al. 2022

Pharmacology Res & Perspec

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“…To date, several studies have confirmed that MPA is secreted in saliva and have shown a good correlation between saliva and plasma MPA exposures [8,16,19,20]. However, more recently, two studies have reported contradictory results [15,21]. All studies on salivary MPA (sMPA) have employed liquid chromatography tandem mass spectrometry (LC-MS/ MS) for sMPA determination [8,15,16,19,20,22], but none have used high-performance liquid chromatography with fluorescence detection (HPLC-FLD).…”

Section: Introductionmentioning

confidence: 99%

High-performance liquid chromatography with fluorescence detection for mycophenolic acid determination in saliva samples

et al. 2023

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Background For therapeutic drug monitoring (TDM) of mycophenolic acid (MPA), which is frequently proposed, saliva might be a suitable and easy-to-obtain biological matrix. The study aimed to validate an HPLC method with fluorescence detection for determining mycophenolic acid in saliva (sMPA) in children with nephrotic syndrome. Methods The mobile phase was composed of methanol and tetrabutylammonium bromide with disodium hydrogen phosphate (pH 8.5) at a 48:52 ratio. To prepare the saliva samples, 100 µL of saliva, 50 µL of calibration standards, and 50 µL of levofloxacin (used as an internal standard) were mixed and evaporated to dryness at 45 °C for 2 h. The resulting dry extract was reconstituted in the mobile phase and injected into the HPLC system after centrifugation. Saliva samples from study participants were collected using Salivette® devices. Results The method was linear within the range of 5–2000 ng/mL, was selective with no carry-over effect and met the acceptance criteria for within-run and between-run accuracy and precision. Saliva samples can be stored for up to 2 h at room temperature, for up to 4 h at 4 °C, and for up to 6 months at − 80 °C. MPA was stable in saliva after three freeze–thaw cycles, in dry extract for 20 h at 4 °C, and for 4 h in the autosampler at room temperature. MPA recovery from Salivette® cotton swabs was within the range of 94–105%. The sMPA concentrations in the two children with nephrotic syndrome who were treated with mycophenolate mofetil were within 5–112 ng/mL. Conclusions The sMPA determination method is specific, selective, and meets the validation requirements for analytic methods. It may be used in children with nephrotic syndrome; however further studies are required to investigate focusing on sMPA and the correlation between sMPA and total MPA and its possible contribution to MPA TDM is required. Graphical abstract

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Liquid chromatography–tandem mass spectrometry method for mycophenolic acid and its glucuronide determination in saliva samples from children with nephrotic syndrome

Sobiak,

Resztak,

Sikora

et al. 2024

Pharmacol. Rep

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Background Saliva sampling is one of the methods of therapeutic drug monitoring for mycophenolic acid (MPA) and its metabolite, mycophenolic acid glucuronide (MPAG). The study describes the liquid chromatography tandem mass spectrometry (LC–MS/MS) method developed for saliva MPA and MPAG determination in children with nephrotic syndrome. Methods The mobile phase consisted of methanol and water at gradient flow, both with 0.1% formic acid. Firstly, 100 µL of saliva was evaporated at 45 °C for 2 h to dryness, secondly, it was reconstituted in the mobile phase, and finally 10 µL was injected into the LC–MS/MS system. Saliva from ten children with nephrotic syndrome treated with mycophenolate mofetil was collected with Salivette®. Results For MPA and MPAG, within the 2–500 ng/mL range, the method was selective, specific, accurate and precise within-run and between-run. No carry-over and matrix effects were observed. Stability tests showed that MPA and MPAG were stable in saliva samples if stored for 2 h at room temperature, 18 h at 4 °C, and at least 5 months at − 80 °C as well as after three freeze–thaw cycles, in a dry extract for 16 h at 4 °C, and for 8 h at 15 °C in the autosampler. The analytes were not adsorbed onto Salivette® cotton swabs. For concentrations above 500 ng/mL, the samples may be diluted twofold. In children, saliva MPA and MPAG were within the ranges of 4.6–531.8 ng/mL and 10.7–183.7 ng/mL, respectively. Conclusions The evaluated LC–MS/MS method has met the validation requirements for saliva MPA and MPAG determination in children with nephrotic syndrome. Further studies are needed to explore plasma–saliva correlations and assess their potential contribution to MPA monitoring. Graphical abstract

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Comparison of free plasma versus saliva mycophenolic acid exposure following mycophenolate mofetil administration in adult kidney transplant recipients

Cited by 3 publications

References 13 publications

Utility of salivary mycophenolic acid concentration monitoring: Modeling and Monte Carlo validation approach

Utility of salivary mycophenolic acid concentration monitoring: Modeling and Monte Carlo validation approach

High-performance liquid chromatography with fluorescence detection for mycophenolic acid determination in saliva samples

Liquid chromatography–tandem mass spectrometry method for mycophenolic acid and its glucuronide determination in saliva samples from children with nephrotic syndrome

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