Population pharmacokinetics of mycophenolic acid in Mexican patients with lupus nephritis
Autor: | Melissa Romano-Aguilar, Carlos Abud-Mendoza, Juan Eduardo Reséndiz-Galván, Marco Ulises Martínez-Martínez, Silvia Romano-Moreno, Susanna Edith Medellín-Garibay, Rosa del Carmen Milán-Segovia |
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Rok vydání: | 2020 |
Předmět: |
Adult
Male Adolescent medicine.medical_treatment Lupus nephritis Population pharmacokinetics Pharmacology 030226 pharmacology & pharmacy Models Biological Mycophenolic acid 03 medical and health sciences Young Adult 0302 clinical medicine Rheumatology Pharmacokinetics medicine Humans Mexico 030203 arthritis & rheumatology business.industry Middle Aged Mycophenolic Acid medicine.disease Lupus Nephritis Multidrug Resistance-Associated Protein 2 NONMEM Immunosuppressive drug Linear Models Prednisone Drug Therapy Combination Female business Immunosuppressive Agents Software medicine.drug |
Zdroj: | Lupus. 29(9) |
ISSN: | 1477-0962 |
Popis: | BackgroundMycophenolic 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.MethodsBlood 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.ResultsA 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−1and 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.ConclusionsThis 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. |
Databáze: | OpenAIRE |
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