Document
Generically Dependent Continuant
RDF description of Population pharmacokinetics of mycophenolic acid in Mexican patients with lupus nephritis - http://orbis.uaslp.mx/vivo/individual/scopus6470
Article
Population pharmacokinetics of mycophenolic acid in Mexican patients with lupus nephritis
Background: Mycophenolic acid (MPA) is an effective oral immunosuppressive drug used to treat lupus nephritis (LN), which exhibits large pharmacokinetic variability. This study aimed to characterize MPA pharmacokinetic behaviour in Mexican LN patients and to develop a population pharmacokinetic model which identified factors that influence MPA pharmacokinetic variability. Methods: Blood samples from LN patients treated with mycophenolate mofetil (MMF) were collected pre dose and up to six hours post dose. MPA concentrations were determined by a validated ultra-performance liquid chromatography tandem mass spectrometry technique. Patients were genotyped for polymorphisms in enzymes (UGT1A8, 1A9 and 2B7) and transporters (ABCC2 and SLCO1B3). The anthropometric, clinical, genetic and co-medication characteristics of each patient were considered as potential covariates to explain the variability. Results: A total of 294 MPA concentrations from 40 LN patients were included in the development of the model. The data were analysed using NONMEM software and were best described by a two-compartment linear model. MPA CL, Vc, Vp, Ka and Q were 15.4 L/h, 22.86 L, 768 L, 1.28 h−1 and 20.3 L/h, respectively. Creatinine clearance and prednisone co-administration proved to have influence on clearance, while body weight influenced Vc. The model was internally validated, proving to be stable. MMF dosing guidelines were obtained through stochastic simulations performed with the final model. Conclusions: This is the first MPA population pharmacokinetic model to have found that co-administration of prednisone results in a considerable increase on clearance. Therefore, this and the other covariates should be taken into account when prescribing MMF in order to optimize the immunosuppressant therapy in patients with LN. © The Author(s) 2020.
immunosuppressant; lupus nephritis; mycophenolic acid (MPA); NONMEM; Population pharmacokinetics glucuronosyltransferase 1A8; glucuronosyltransferase 1A9; glucuronosyltransferase 2B7; multidrug resistance associated protein 2; mycophenolate mofetil; prednisone; solute carrier organic anion transporter 1B3; tacrolimus; adult; anthropometry; area under the curve; Article; blood sampling; body weight; central volume of distribution; clinical article; clinical feature; creatinine clearance; drug blood level; drug clearance; female; gene frequency; human; immunosuppressive treatment; lupus erythematosus nephritis; male; Mexican; pharmacogenetic testing; pharmacogenetics; plasma concentration-time curve; population research; practice guideline; prescription; priority journal; single nucleotide polymorphism; ultra performance liquid chromatography; vital capacity
multidrug resistance associated protein 2, 256503-65-8; mycophenolate mofetil, 116680-01-4, 128794-94-5; prednisone, 53-03-2; tacrolimus, 104987-11-3
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