PharmGKB summary

Lamba, Vishal; Sangkuhl, Katrin; Sanghavi, Kinjal; Fish, Alyssa; Altman, Russ B.; Klein, Teri E.

doi:10.1097/fpc.0000000000000010

Cited by 68 publications

(39 citation statements)

References 62 publications

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“…Mycophenolate mofetil is the prodrug of the active mycophenolic acid (MPA). It is metabolized by carboxylesterase 2 (CES2), after which MPA is further metabolized by several CYPs and UGTs [ 113 ]. MPA-glucuronide is excreted in the bile primarily by ABCC2 (encoded by ABCC2 ) and this transport is essential for enterohepatic circulation.…”

Section: Pharmacokinetic and Pharmacogenetic Studies Of Relevant Membmentioning

confidence: 99%

Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics

et al. 2015

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Membrane transporters play an essential role in the transport of endogenous and exogenous compounds, and consequently they mediate the uptake, distribution, and excretion of many drugs. The clinical relevance of transporters in drug disposition and their effect in adults have been shown in drug–drug interaction and pharmacogenomic studies. Little is known, however, about the ontogeny of human membrane transporters and their roles in pediatric pharmacotherapy. As they are involved in the transport of endogenous substrates, growth and development may be important determinants of their expression and activity. This review presents an overview of our current knowledge on human membrane transporters in pediatric drug disposition and effect. Existing pharmacokinetic and pharmacogenetic data on membrane substrate drugs frequently used in children are presented and related, where possible, to existing ex vivo data, providing a basis for developmental patterns for individual human membrane transporters. As data for individual transporters are currently still scarce, there is a striking information gap regarding the role of human membrane transporters in drug therapy in children.Electronic supplementary materialThe online version of this article (doi:10.1007/s40262-015-0328-5) contains supplementary material, which is available to authorized users.

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Section: Pharmacokinetic and Pharmacogenetic Studies Of Relevant Membmentioning

confidence: 99%

Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics

et al. 2015

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“…Meanwhile, another study revealed no significant changes in pharmacokinetic parameters of TAC and MMF 13 . The reason for the ongoing and decades-long controversy concerning the drug-drug interaction between TAC and MMF seems to be due to a few drug metabolizing enzymes or transporters commonly involved in the metabolic pathway of both drugs 14 , 15 . The cytochrome P450 3A5 ( CYP3A5 ) genotype markedly influences the pharmacokinetics of TAC, while uridine glucuronosyl transferase (UGT) and solute carrier organic anion transporter (SLCO) genotypes have been related with significantly increased dose-adjusted mycophenolic acid (MPA) trough levels 16 – 18 .…”

Section: Introductionmentioning

confidence: 99%

Increased Exposure of Tacrolimus by Co-administered Mycophenolate Mofetil: Population Pharmacokinetic Analysis in Healthy Volunteers

Kim

Han

Kim

et al. 2018

Sci Rep

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The objective of the study was to investigate the pharmacokinetic drug-drug interactions between tacrolimus (TAC) and mycophenolate mofetil (MMF) in healthy Korean male volunteers. Seventeen volunteers participated in a three-period, single-dose, and fixed sequence study. They sequentially received MMF, TAC, and the combination. Concentrations of TAC, mycophenolic acid (MPA), and its metabolites MPA 7-O-glucuronide and MPA acyl glucuronide were measured. The variants of CYP3A4, CYP3A5, SLCO1B1, SLCO1B3, ABCC2, UGT1A9, and UGT2B7 were genotyped. Drug interaction was evaluated with a non-compartmental analysis and population pharmacokinetic modelling to quantify the interaction effect. A total of 1,082 concentrations of those analytes were analysed. AUC0-inf of TAC increased by 22.1% (322.4 ± 174.1 to 393.6 ± 121.7 ng·h/mL; P < 0.05) when co-administered with MMF, whereas the pharmacokinetic parameters of MPA and its metabolites were not changed by TAC. Apparent clearance (CL/F) of TAC was 17.8 L/h [relative standard error (RSE) 11%] or 13.8 L/h (RSE 11%) without or with MMF, respectively. Interaction was explained by the exponential model. The CYP3A5 genotype was the only significant covariate. The population estimate of CL/F of TAC was 1.48-fold (RSE 16%) in CYP3A5 expressers when compared to nonexpressers. CL/F of TAC was decreased when co-administered with MMF in these subjects.

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“…A prodrug of mycophenolic acid, MMF causes depletion of guanosine and deoxyguanosine in both T and B lymphocyte lines via inhibition of inosine-5′monophosphate dehydrogenase (type II), an enzyme that facilitates the production of an intermediate metabolite of guanosine. 52 Net effects include the inhibition of de novo purine synthesis and the suppression of DNA synthesis with subsequent interference in both T and B lymphocyte proliferation, decrease in cytotoxic T cell activity and diminished antibody formation. [53][54][55] Promising results have been reported in the setting of many immunemediated neurological illnesses including NMOSD.…”

Section: Mycophenolate Mofetilmentioning

confidence: 99%

<p>Management Strategies of Patients with Neuromyelitis Optica Spectrum Disorder During the COVID-19 Pandemic Era</p>

Hamdy¹,

Naseer²,

Shehata³

et al. 2020

TCRM

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The ongoing coronavirus (COVID-19) pandemic is a global health emergency of international concern and has affected management plans of many autoimmune disorders. Immunosuppressive and immunomodulatory therapies are pivotal in the management of neuromyelitis optica spectrum disorder (NMOSD), potentially placing patients at an increased risk of contracting infections such as COVID-19. The optimal management strategy of NMOSD during the COVID-19 era remains unclear. Here, however, we examined the evidence of NMOSD disease-modifying therapies (DMTs) use during the present period and highlighted different scenarios including treatment of relapses as well as initiation and maintenance of DMTs in order to optimize care of NMOSD patients in the COVID-19 era.

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PharmGKB summary

Cited by 68 publications

References 62 publications

Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics

Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics

Increased Exposure of Tacrolimus by Co-administered Mycophenolate Mofetil: Population Pharmacokinetic Analysis in Healthy Volunteers

<p>Management Strategies of Patients with Neuromyelitis Optica Spectrum Disorder During the COVID-19 Pandemic Era</p>

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