Pharmacokinetic-pharmacodynamic modelling and simulation of methotrexate dosing in patients with rheumatoid arthritis

被引:0
|
作者
Tan, Jiun Ming [1 ]
Upton, Richard N. [2 ]
Foster, David J. R. [3 ]
Proudman, Susanna M. [4 ,5 ]
Dhir, Varun [6 ]
Wiese, Michael D. [1 ]
机构
[1] Univ South Australia, Ctr Pharmaceut Innovat, UniSA Clin & Hlth Sci, Adelaide, SA, Australia
[2] Univ South Australia, Australian Ctr Pharmacometr, Adelaide, SA, Australia
[3] Univ South Australia, Australian Ctr Precis Hlth, Clin & Hlth Sci, Adelaide, SA, Australia
[4] Royal Adelaide Hosp, Adelaide, SA, Australia
[5] Univ Adelaide, Discipline Med, Adelaide, Australia
[6] Post Grad Inst Med Educ & Res, Dept Internal Med, Clin Immunol & Rheumatol Unit, Chandigarh, India
关键词
methotrexate; parenteral route; population pharmacokinetic-pharmacodynamic modelling; precision dosing; rheumatoid arthritis; simulation; RED-BLOOD-CELLS; POLYGLUTAMATE CONCENTRATIONS; POPULATION PHARMACOKINETICS; ORAL METHOTREXATE; DISEASE-ACTIVITY; ROUTE; THERAPY; DOSAGE; POLYMORPHISMS; DETERMINANTS;
D O I
10.1111/bcp.16158
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
AimsTo develop a non-linear mixed-effects population pharmacokinetic and pharmacodynamic (PK-PD) model describing the change in the concentration of methotrexate polyglutamates in erythrocytes (ery-MTX-PGn with "n" number of glutamate, representing PK component) and how this relates to modified 28-joint Disease Activity Score incorporating erythrocyte sedimentation rate (DAS-28-3) for rheumatoid arthritis (RA), representing PD component.MethodsAn existing PK model was fitted to data from a study consisting of 117 RA patients. The estimation of population PK-PD parameters was performed using stochastic approximation expectation maximisation algorithm in Monolix 2021R2. The model was used to perform Monte Carlo simulations of a loading dose regimen (50mg subcutaneous methotrexate as loading doses, then 20mg weekly oral methotrexate) compared to a standard dosing regimen (10mg weekly oral methotrexate for 2 weeks, then 20mg weekly oral methotrexate).ResultsEvery 40 nmol/L increase in ery-MTX-PG3-5 total concentration correlated with 1-unit reduction in DAS-28-3. Significant covariate effects on the therapeutic response of methotrexate included the use of prednisolone in the first 4 weeks (positive use correlated with 25% reduction in DAS-28-3 when other variables were constant) and patient age (every 10-year increase in age correlated with 3.4% increase in DAS-28-3 when other variables were constant). 4 methotrexate loading doses led to a higher percentage of patients achieving a good/moderate response compared to the standard regimen (Week 4: 87.6% vs. 39.8%; Week 10: 64.7% vs. 57.0%).ConclusionsA loading dose regimen was more likely to achieve higher ery-MTX-PG concentration and better therapeutic response after 4 weeks of methotrexate treatment.
引用
收藏
页码:2763 / 2780
页数:18
相关论文
共 50 条
  • [31] Pharmacokinetic-pharmacodynamic modelling of antibiotic therapy in severe sepsis
    Duszynska, Wieslawa
    ANAESTHESIOLOGY INTENSIVE THERAPY, 2012, 44 (03) : 158 - 164
  • [32] Evaluation of etanercept dose reduction in patients with rheumatoid arthritis using pharmacokinetic/pharmacodynamic modeling and simulation
    Hsu, Li-feng
    Huang, Jin-ding
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS, 2014, 52 (09) : 776 - 786
  • [33] PHARMACOKINETIC-PHARMACODYNAMIC MODELLING OF ARTESUNATE IN PATIENTS WITH DRUG RESISTANT AND SENSITIVE MALARIA (TRAC)
    Hoglund, Richard
    AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2018, 99 (04): : 443 - 443
  • [34] Pharmacokinetic-Pharmacodynamic Modeling of Fostamatinib Efficacy on ACR20 to Support Dose Selection in Patients With Rheumatoid Arthritis (RA)
    Maringwa, John
    Kagedal, Matts
    Hamren, Ulrika Wahlby
    Martin, Paul
    Cox, Eugene
    Hamren, Bengt
    JOURNAL OF CLINICAL PHARMACOLOGY, 2015, 55 (03): : 328 - 335
  • [35] Revising Pediatric Vancomycin Dosing Accounting for Nephrotoxicity in a Pharmacokinetic-Pharmacodynamic Model
    Kloprogge, Frank
    Hill, Louise F.
    Booth, John
    Klein, Nigel
    Irwin, Adam D.
    Dixon, Garth
    Standing, Joseph F.
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2019, 63 (05)
  • [36] PULSE DOSING VERSUS CONTINUOUS INFUSION OF ANTIBIOTICS - PHARMACOKINETIC-PHARMACODYNAMIC CONSIDERATIONS
    LEBEL, M
    SPINO, M
    CLINICAL PHARMACOKINETICS, 1988, 14 (02) : 71 - 95
  • [37] Pharmacokinetic-pharmacodynamic rationale for cefepime dosing regimens in intensive care units
    Roos, Juliana F.
    Bulitta, Jurgen
    Lipman, Jeffrey
    Kirkpatrick, Carl M. J.
    JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2006, 58 (05) : 987 - 993
  • [38] Translational Pharmacokinetic-Pharmacodynamic Modeling and Simulation: Optimizing 5-Fluorouracil Dosing in Children With Pediatric Ependymoma
    Daryani, V. M.
    Patel, Y. T.
    Tagen, M.
    Turner, D. C.
    Carcaboso, A. M.
    Atkinson, J. M.
    Gajjar, A.
    Gilbertson, R. J.
    Wright, K. D.
    Stewart, C. F.
    CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, 2016, 5 (04): : 211 - 221
  • [39] Quantifying the Effect of Methotrexate on Adalimumab Response in Psoriasis by Pharmacokinetic-Pharmacodynamic Modeling
    van Huizen, Astrid
    Bank, Paul
    van der Kraaij, Gayle
    Musters, Annelie
    Busard, Celine
    Menting, Stef
    Rispens, Theo
    de Vries, Annick
    van Doorn, Martijn
    Prens, Errol
    Lambert, Jo
    van den Reek, Juul
    de Jong, Elke
    Mathot, Ron
    Spuls, Phyllis
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2024, 144 (04)
  • [40] Lack of pharmacokinetic interaction of meloxicam with methotrexate in patients with rheumatoid arthritis
    Hubner, G
    Sander, O
    Degner, FL
    Turck, D
    Rau, R
    JOURNAL OF RHEUMATOLOGY, 1997, 24 (05) : 845 - 851