Nonlinear relationship between enteric-coated mycophenolate sodium dose and mycophenolic acid exposure in Han kidney transplantation recipients

Zhang, Jun; Jia, Mengmeng; Zuo, Li; Li, Na; Luo, Yi; Sun, Zhi; Zhang, Xiaojian; Zhu, Zhenfeng

doi:10.1016/j.apsb.2016.11.003

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…Short-term stability at − 80 °C demonstrates that MPA and MPAG were stabled under this condition. Besides that, it has already been described in the literature that samples are stable in plasma at − 80 °C for at least 6 months, so kidneytransplanted samples were kept at this condition until analysis [10,13,19,24].…”

Section: Bioanalytical Methods Validationmentioning

confidence: 99%

“…In this study, to determinate and oral fluid concentrations of MPA and MPAG, the validated LC-MS method was applied to samples from 13 kidney transplant patients. To analyse the results, a non-compartmental model was used as it has already been described for MPA and MPAG in several studies [17,19,[25][26][27]. The plasma and oral fluid concentrations of MPA and MPAG were found to be variable for both analytes (Fig.…”

Section: Pharmacokinetics Analysismentioning

confidence: 99%

“…Methods to detect MPA and its glucuronide metabolite in a different biological matrix have already been described, but there has only been one study using oral fluid to detect MPAG [8,13,15,[17][18][19][20]. This study aimed to develop a sensitive LC-MS method with a simple and rapid sample clean up to quantify MPA and MPAG in oral fluid and plasma in order to apply it in samples from kidney transplant patients using a limited sampling strategy and try to establish a correlation between them.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of plasma and oral fluid concentrations of mycophenolic acid and its glucuronide metabolite by LC-MS in kidney transplant patients

Ferreira

Thiesen

Araújo

et al. 2019

Eur J Clin Pharmacol

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Purpose Mycophenolic acid is one of the most used immunosuppressive drugs in solid organ transplant treatments in the world. Developing a highly sensitive analytical method to analyse the drug and its metabolites in oral fluid and plasma is important to evaluate the possibility of using oral fluid as a biological matrix in therapeutic drug monitoring, instead of plasma. Method The liquid chromatography coupled to mass spectrometry (LC-MS) method was developed and validated for determining mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) in oral fluid and plasma, with both matrices presenting a detection limit of 1 ng/mL for MPA and 5 ng/mL for MPAG. Both analytes were analysed after a simple protein precipitation procedure. Transplanted-kidney samples of oral fluid and blood were collected from 13 patients that were hospitalised and kept at − 80 °C until analyses. Results The proposed method was linear in the concentration range of 5-500 ng/mL for MPA and 10-500 ng/mL for MPAG, with correlation coefficients (r) between 0.9925 and 0.9973. It was then applied to samples collected from kidney-transplanted patients and used for calculation of pharmacokinetics parameters. Conclusion After comparing plasma and oral fluid concentrations as well as performing a non-compartmental pharmacokinetic analysis of the average curves, it is possible to suggest that oral fluid concentration may be used as an alternative for MPA and MPAG monitoring in kidney transplant patients.

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Section: Bioanalytical Methods Validationmentioning

confidence: 99%

Section: Pharmacokinetics Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparison of plasma and oral fluid concentrations of mycophenolic acid and its glucuronide metabolite by LC-MS in kidney transplant patients

Ferreira

Thiesen

Araújo

et al. 2019

Eur J Clin Pharmacol

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“…The blood samples were centrifuged at 3000 r/min and plasma samples were separated. MPA concentrations were analyzed using the validated ultra-performance liquid chromatography ultraviolet (UPLC-UV) method ( Zhang et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of Mycophenolate Mofetil and Development of Limited Sampling Strategy in Early Kidney Transplant Recipients

et al. 2018

Self Cite

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The mycophenolate mofetil (MMF) dose management for optimization of post-transplant treatment especially the early postoperative phase has been well recognized. MMF is a pro-drug of mycophenolic acid (MPA) and is widely used in Chinese renal transplant patients. Until now, the pharmacokinetic (PK) characteristics and model for the area under the concentration–time curve for the 12-h (h) of exposure (AUC0-12 h) of MPA (MPA-AUC0-12 h) estimation were lacking for the new formulation of MMF dispersible tablet in renal transplant patients. The aims of the study were to investigate the PK characteristics of MMF dispersible tablet by detecting the active metabolite of MPA and to establish an accuracy and precision equation for calculating MPA-AUC0-12 h by limited sampling strategy (LSS) in Chinese kidney transplant patients. A total of 60 postoperative kidney transplant recipients were given a multiple-dose of MMF dispersible tablet twice daily combination with tacrolimus (Tac) and steroids. On the 5th day post-transplantation, blood specimens were collected before drug administration and up to 12 h after MMF dispersible tablet administration. Non-compartmental PK analysis was used to determine the data obtained from individual patients. Multivariate stepwise regression analysis was used to develop models for predicting MPA-AUC0-12 h. The 3- and 4-point sampling models using 2 h, 4 h, 8 h and 1 h, 2 h, 4 h and 8 h, respectively, allowed accurate estimation of MPA-AUC0-12 h. PK parameters of MMF dispersible tablet were obtained and the 4-point LSS is the best model for accurate and precise estimation of MPA-AUC0-12 h.

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“…An analysis of the quality of interactions of the 10 best compounds revealed that Simeprevir had the highest number of polar bonds with side chains of residues in the RBD binding pocket. Simeprevir, a second-generation HCV NS3/4A protease inhibitor 28 , has been reported to be both a SARS-CoV-2 main protease inhibitor 29 and a S protein-RBD interaction inhibitor 30 . Simeprevir forms an extended network of H-bonds with Arg403, Lys417, Gln493, Gly496 and Tyr505, and forms Van Der Waals interactions with Tyr421, Tyr453 and Tyr505 (Fig.…”

Section: Resultsmentioning

confidence: 99%

An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors

Trezza

Iovinelli

Santucci

et al. 2020

Sci Rep

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The Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The virus has rapidly spread in humans, causing the ongoing Coronavirus pandemic. Recent studies have shown that, similarly to SARS-CoV, SARS-CoV-2 utilises the Spike glycoprotein on the envelope to recognise and bind the human receptor ACE2. This event initiates the fusion of viral and host cell membranes and then the viral entry into the host cell. Despite several ongoing clinical studies, there are currently no approved vaccines or drugs that specifically target SARS-CoV-2. Until an effective vaccine is available, repurposing FDA approved drugs could significantly shorten the time and reduce the cost compared to de novo drug discovery. In this study we attempted to overcome the limitation of in silico virtual screening by applying a robust in silico drug repurposing strategy. We combined and integrated docking simulations, with molecular dynamics (MD), Supervised MD (SuMD) and Steered MD (SMD) simulations to identify a Spike protein-ACE2 interaction inhibitor. Our data showed that Simeprevir and Lumacaftor bind the receptorbinding domain of the Spike protein with high affinity and prevent ACE2 interaction. The World Health Organisation (WHO) declared the Coronavirus disease (COVID-19) outbreak a pandemic on March 12th 2020, and as of May 21st, over 4,893,186 cases and 323,256 deaths have been reported (https :// www.who.int/emerg encie s/disea ses/novel-coron aviru s-2019/situa tion-repor ts/). The Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was identified as the viral agent causing the disease. SARS-CoV-2 is closely related to the SARS-CoV, which caused a pandemic in 2002-2003 1 , and it is believed to be the third member of the Coronaviridae family to cause severe respiratory diseases in human 2. Despite several ongoing clinical studies, there are currently no approved vaccines or drugs that specifically target SARS-CoV-2. SARS-CoV-2 has a single-stranded positive-sense RNA composed of 29,903 nt containing five genes, ORF1ab (codifying 16 non-structural proteins), spike (S), envelope (E), membrane (M) and nucleocapsid (N) genes 3. The virus uses the S homotrimeric glycoprotein located on the virion surface to allow entry into the human cells 4. The S protein goes through major structural rearrangements to mediate viral and human cell membranes fusion. The process is initiated by the binding of the receptor-binding domain (RBD) of the S1 subunit to the peptidase domain (PD) of angiotensin-converting enzyme 2 receptor (ACE2) on the host cell 5. Structural studies have shown that two S protein trimers can simultaneously bind to one ACE2 dimer 6. This induces a conformational change that expose a proteolytic site on the S protein, which is cleaved by the cellular serine protease TMPRSS2 7. Dissociation of S1 induces transition of the S2 subunit to a post fusion conformation, with exposed fusion peptides 8 , which allows endocytic entry of virus 9. Wrapp et ...

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Nonlinear relationship between enteric-coated mycophenolate sodium dose and mycophenolic acid exposure in Han kidney transplantation recipients

Cited by 7 publications

References 29 publications

Comparison of plasma and oral fluid concentrations of mycophenolic acid and its glucuronide metabolite by LC-MS in kidney transplant patients

Comparison of plasma and oral fluid concentrations of mycophenolic acid and its glucuronide metabolite by LC-MS in kidney transplant patients

Pharmacokinetics of Mycophenolate Mofetil and Development of Limited Sampling Strategy in Early Kidney Transplant Recipients

An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors

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