Simplification of a pharmacokinetic model for red blood cell methotrexate disposition.
Purpose: A pharmacokinetic (PK) model is available for describing the time course of the concentrations of methotrexate (MTX or MTXGlu) and its active polyglutamated metabolites (MTXGlu) in red blood cells (RBCs). In this study, we aimed to simplify the MTX PK model and to optimise the blood samplin...
| Published in: | European Journal of Clinical Pharmacology Vol. 71; no. 12; pp. 1509 - 1517 |
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| Main Authors: | , , , |
| Format: | research tables/charts Journal Article |
| Published: |
Springer Nature
Dec2015
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=110901323&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 110901323 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Dec2015 vid: 71 iid: 12 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 110901323 110901323 110901323 10.1007/s00228-015-1951-7 NLM26407686 110901323 ppf: 1509 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Simplification of a pharmacokinetic model for red blood cell methotrexate disposition. aug: au: Pan, Shan Korell, Julia Stamp, Lisa Duffull, Stephen affil: School of Pharmacy, University of Otago, Dunedin New Zealand sug: subj: Erythrocytes Metabolism Methotrexate Pharmacokinetics Methotrexate Metabolism Human Arthritis, Rheumatoid Drug Therapy Software ab: Purpose: A pharmacokinetic (PK) model is available for describing the time course of the concentrations of methotrexate (MTX or MTXGlu) and its active polyglutamated metabolites (MTXGlu) in red blood cells (RBCs). In this study, we aimed to simplify the MTX PK model and to optimise the blood sampling schedules for use in future studies. Methods: A proper lumping technique was used to simplify the original MTX RBC PK model. The sum of predicted RBC MTXGlu concentrations in both the simplified and original models was compared. The sampling schedules for MTXGlu or all MTX polyglutamates in RBCs were optimised using the Population OPTimal design (POPT) software. Results: The MTX RBC PK model was simplified into a three-state model. The maximum of the absolute value of relative difference in the sum of predicted RBC MTXGlu concentrations over time was 6.3 %. A five blood sample design was identified for estimating parameters of the simplified model. Conclusions: This study illustrates the application of model simplification processes to an existing model for MTX RBC PK. The same techniques illustrated in our study may be adopted by other studies with similar interest. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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