ArticleBritish journal of clinical pharmacology2026
Pharmacokinetic profiling of imatinib in relation to CYP3A4 activity in leukaemia patients.
Article in British journal of clinical pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Pharmacokinetic profiling of imatinib in relation to CYP3A4 activity in leukaemia patients.British journal of clinical pharmacology · 2026Article
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15 authors.
Funding
Abstract
aimImatinib pharmacokinetics exhibit large interindividual variability because of differences in CYP3A4 activity-the main imatinib-metabolizing enzyme. While therapeutic drug monitoring is effective, it requires steady-state conditions and frequent sampling. The endogenous biomarker 4β-hydroxycholesterol (4-β-OHC) has been proposed to reflect CYP3A4 activity, enabling proactive dose optimization. This study investigated 4-β-OHC as a CYP3A4 biomarker in leukaemia patients and its relationship with imatinib pharmacokinetics
methodsA pharmacokinetic study included 19 patients with chronic myeloid leukaemia or acute lymphoblastic leukaemia receiving imatinib. Blood samples were collected over 24 h. Imatinib, N-desmethyl imatinib, 4-β-OHC and 4α-hydroxycholesterol (4-α-OHC) plasma concentrations were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), while total cholesterol was measured by clinical chemistry autoanalyser. CYP3A4 activity was estimated using the 4-β-OHC/cholesterol ratio. Genotyping of relevant CYP3A4/5 gene variants was carried out. Pharmacokinetic parameters were estimated using PKanalix software. Simple and multiple linear regressions were performed
resultsNineteen patients were included with median age of 66 years (range 44-77). Pharmacokinetic parameters were comparable to prior reporting. The 4-β-OHC/cholesterol ratio showed a significant positive association with imatinib clearance, explaining 30% of variance. No significant association was found between CYP3A4 activity and N-desmethyl-imatinib area under the concentration time-curve (AUC)/imatinib AUC ratio. Single-point sampling of imatinib at 3-4 h post-dose correlated better with AUC
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