Population pharmacokinetic modelling of imatinib in healthy subjects receiving a single dose of 400 mg.
Purpose: Imatinib is indicated for treatment of CML, GIST, etc. The population pharmacokinetics (popPK) of imatinib in patients under long-term treatment are reported in literature. Data obtained from bioequivalence trials for healthy subjects were used to evaluate the influence of demographic and p...
| Publicado en: | Cancer Chemotherapy & Pharmacology Vol. 90; no. 2; pp. 125 - 137 |
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| Autores principales: | , , , , , , , , |
| Formato: | equations & formulas research tables/charts Journal Article |
| Publicado: |
Springer Nature
Aug2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=158429735&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 158429735 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03445704 NO9 jtl: Cancer Chemotherapy & Pharmacology issn: 03445704 maglogo: N pubinfo: dt: Aug2022 vid: 90 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 158429735 157951169 158429735 NLM35831644 158429735 10.1007/s00280-022-04454-y NLM35831644 158429735 ppf: 125 ppct: 12 formats: tig: atl: Population pharmacokinetic modelling of imatinib in healthy subjects receiving a single dose of 400 mg. aug: au: Chien, Yi-Han Würthwein, Gudrun Zubiaur, Pablo Posocco, Bianca Pena, María Ángeles Borobia, Alberto M. Gagno, Sara Abad-Santos, Francisco Hempel, Georg affil: Westfälische Wilhelms-Universität Münster, Institut für Pharmazeutische und Medizinische Chemie-Klinische Pharmazie, Corrensstraße 48, 48149, Münster, Germany sug: subj: Gastrointestinal Neoplasms Drug Therapy Research Subjects Kinetics Pharmacokinetics Models, Biological Human ab: Purpose: Imatinib is indicated for treatment of CML, GIST, etc. The population pharmacokinetics (popPK) of imatinib in patients under long-term treatment are reported in literature. Data obtained from bioequivalence trials for healthy subjects were used to evaluate the influence of demographic and pharmacogenetic factors on imatinib pharmacokinetics (PK) in a collective without concurrent drugs, organ dysfunction, inflammation etc. In addition, the differences in PK between the healthy subjects and a patient cohort was examined to identify possible disease effects.Methods: 26 volunteers were administered orally with single dose of 400 mg imatinib. 16-19 plasma samples per volunteer were collected from 0.5 up to 72 h post-dose. The popPK was built and post hoc estimates were compared with previously published PK parameters evaluated by non-compartmental analysis in the same cohort. The predictivity of the model for data collected from 40 patients with gastrointestinal stromal tumors at steady state was evaluated.Results: The popPK was best described by a two-compartment transit model with first-order elimination. No significant covariates were identified, probably due to the small cohort and the narrow range of demographic covariates; CYP3A5 phenotypes appeared to have some influence on the clearance of imatinib. Good agreement between non-compartment and popPK analyses was observed with the differences of the geometric means/ median of PK estimates below 10%. The model indicated lower clearance for patients compared to healthy volunteers (p value < 0.01).Conclusion: The two-compartment transit model adequately describes the absorption and distribution of imatinib in healthy volunteers. For patients, a lower clearance of imatinib compared to healthy volunteer was estimated by the model. The model can be applied for dose individualization based on trough concentrations assuming no significant differences in absorption between patients and healthy volunteers. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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