Overview of therapeutic drug monitoring of immunosuppressive drugs: Analytical and clinical practices

Seyfinejad, Behrouz; Jouyban, Abolghasem

doi:10.1016/j.jpba.2021.114315

Cited by 19 publications

(6 citation statements)

References 192 publications

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“…MPA has largely replaced azathioprine, another antiproliferative agent. Compared to azathioprine, MPA is a stronger immunosuppressant with improved graft survival (Knight et al., 2009; Seyfinejad & Jouyban, 2021; Wagner et al., 2015). MPA is administered as mycophenolate mofetil (MPA ester), and its side effects include diarrhea, vomiting, nausea, and abdominal pain.…”

Section: Commentarymentioning

confidence: 99%

“…Underdosing can result in organ rejection, and overdosing can result in bone marrow suppression and an increased risk of infections. Therefore, therapeutic drug monitoring for MPA and its major metabolite MPAG is needed (Seyfinejad & Jouyban, 2021; Winnicki et al., 2022).…”

Section: Commentarymentioning

confidence: 99%

“…There are various methods for the quantification of MPA and MPAG levels. These include immunassays, HPLC linked to an ultraviolet detector (HPLC/UV) and HPLC linked to a tandem mass spectrometer (HPLC‐MS/MS) (Danafar & Hamidi, 2015; Glahn‐Martinez et al., 2018; Kikuchi et al., 2018; Klepacki et al., 2012; Kunicki et al., 2015; Liu et al., 2021; Seyfinejad & Jouyban, 2021; Zhou et al., 2021). LC‐MS/MS is the most commonly used method for the quantification of MPA followed by immunoassays (College of American Pathologists Surveys, 2022).…”

Section: Commentarymentioning

confidence: 99%

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Quantitation of Mycophenolic Acid and Mycophenolic Acid Glucuronide in Serum or Plasma by LC‐MS/MS

2023

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Mycophenolic acid (MPA) is an immunosuppressant that is used as an adjunct therapy in renal, liver, and heart transplantation. Due to its narrow therapeutic range, monitoring MPA levels is essential to avoid toxicity and organ rejection. Although immunoassays are available for the determination of MPA, mass spectrometry methods are preferred due to their higher specificity. Herein, we describe a liquid chromatography tandem mass spectrometry (LC-MS/MS) method utilizing positive ionization electrospray and multiple reaction monitoring (MRM) for the quantification of MPA levels and its conjugate, MPA glucuronide (MPAG). Blood collected in a plain, EDTA, or heparin-containing tube is centrifuged to separate the serum or plasma. Proteins are precipitated using a zinc sulfate solution and acetonitrile containing deuterated internal standards (MPA-d3 and MPAG-d3). The resulting protein-free supernatant is injected into the LC-MS/MS system for analysis. The chromatography involves the use of a C18 column and ammonium acetate/water/formic acid and ammonium acetate/methanol/formic acid mobile phases. Quantification of MPA and MPAG levels is achieved by comparing the MRM peak area ratios of analytes and internal standards, consisting of specific precursor/product pairs, with those of calibrators at various concentrations. Calibration curves are constructed from the MRM peak area ratios of calibrators and internal standards versus concentration.

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Section: Commentarymentioning

confidence: 99%

Section: Commentarymentioning

confidence: 99%

Section: Commentarymentioning

confidence: 99%

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Quantitation of Mycophenolic Acid and Mycophenolic Acid Glucuronide in Serum or Plasma by LC‐MS/MS

2023

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“…Of these, tacrolimus is the most preferred due to its greater potency, and lesser risks of rejection and nephrotoxicity [ 2 ]. Wide inter-and intra-patient variability, narrow therapeutic window, and the risk of toxicity are the key factors driving therapeutic drug monitoring of these immunosuppressants [ 3 ]. Maintaining drug concentrations in the therapeutic range is crucial for preventing rejection episodes and toxicity amelioration [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants

Sridharan

Shah

Jasim

et al. 2022

JPM

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Cytochrome P450 (CYP) enzymes, such as CYP3A4, and CYP3A5, P450 oxidoreductase (POR), peroxisome proliferator activated receptor alpha (PPAR-alpha), and drug transporter (ABCB1) were observed to influence concentrations of immunosuppressants (cyclosporine, everolimus, sirolimus, and tacrolimus) and outcomes in renal transplants. We carried out the present study to evaluate the prevalence and impact of these single nucleotide polymorphisms (SNPs) in adult renal transplants. SNPs were evaluated using commercial TaqMan® assays. Serum drug concentrations were estimated using immunoassays. One hundred and forty-six patients were recruited. SNPs in CYP3A5*3 were significantly associated with greater dose-adjusted cyclosporine and tacrolimus concentrations. SNPs in POR*28 were observed with significantly lower dose-adjusted concentrations, particularly with cyclosporine and tacrolimus. ABCB1 homozygous polymorphisms were observed with significantly lower time spent in the therapeutic range with cyclosporine and everolimus/sirolimus. Cyclosporine was observed in a significantly greater proportion of patients with elevated GGT, and SNPs in PPAR-alpha were significantly associated with an increased risk of this adverse event. Hypertriglyceridemia with everolimus was significantly associated with POR*28 polymorphisms. There is a need to validate the influence of these SNPs in a prospective study and develop an algorithm predicting the achievement of target concentrations.

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“…Therapeutic drug monitoring (TDM) is essential for optimizing the dosage regimen of drugs with large variations in individual pharmacokinetics, narrow therapeutic windows, and adverse side effects. TDM is widely applied to antineoplastic drugs, [1][2][3][4] immunosuppressive agents, [5][6][7][8][9] antiepileptic drugs, [10][11][12] and antibiotics. [13][14][15] Lenvima (lenvatinib), an oral multikinase inhibitor, has been approved for treating unresectable hepatocellular carcinoma (HCC).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a Capillary Microsampling Device for Analyzing Plasma Lenvatinib Concentration in Patients With Hepatocellular Carcinoma

Saito

Kikuchi

Matsumoto

et al. 2022

Therapeutic Drug Monitoring

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Background:The anticancer drug, Lenvima (lenvatinib), has severe side effects. Therapeutic drug monitoring helps ensure its efficacy and safety. Regular and optimally timed blood sampling is tough, especially when lenvatinib is self-medicated. Microsampling using the easy to handle Microsampling Wing (MSW) may help circumvent this problem. However, current lenvatinib detection methods are not sensitive enough to detect its concentrations in microsamples (,50-250 mL). Thus, the aim of this study was 2-fold (1) develop an analytic method to estimate plasma lenvatinib concentrations in microsamples and (2) verify whether this method works on micro (5.6 mL) blood plasma samples obtained clinically through MSW from patients with unresectable hepatocellular carcinoma (HCC).Methods: A simple, highly sensitive, and specific liquid chromatography-electrospray ionization tandem mass spectrometry method was developed. Using this novel protocol, the trough blood plasma concentration of lenvatinib was measured for both blood sampled conventionally and that using MSW. Thirty-five venous whole blood samples were obtained from 11 patients with HCC. Furthermore, the stability of lenvatinib in MSW samples during storage was evaluated. Results:The mean plasma lenvatinib concentration estimates were not significantly different between the MSW and conventional venous blood samples. CV for interday and intraday assays was low. Up to day 5, the lenvatinib concentration in the MSW samples was 85%-115% of the initial day concentration (when stored at 258C or 48C). The interference of endogenous matrix components in the human plasma was low. Conclusions:These results indicate that the novel mass spectrometry protocol accurately measures lenvatinib in human plasma and is reproducible. Thus, MSW could be a useful microsampling device for lenvatinib therapeutic drug monitoring in patients with HCC when used in combination with this novel liquid chromatographyelectrospray ionization tandem mass spectrometry detection method.

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Overview of therapeutic drug monitoring of immunosuppressive drugs: Analytical and clinical practices

Cited by 19 publications

References 192 publications

Quantitation of Mycophenolic Acid and Mycophenolic Acid Glucuronide in Serum or Plasma by LC‐MS/MS

Quantitation of Mycophenolic Acid and Mycophenolic Acid Glucuronide in Serum or Plasma by LC‐MS/MS

Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants

Evaluation of a Capillary Microsampling Device for Analyzing Plasma Lenvatinib Concentration in Patients With Hepatocellular Carcinoma

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