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- Title
Relationship between trough level of tyrosine kinase inhibitor (imatinib and nilotinib) and BCR-ABL ratios in an Indonesian chronic-phase chronic myeloid leukemia (CML) population.
- Authors
Suprapti, Budi; Andarsari, Mareta Rindang; Hapsari, Pharmasinta Putri; Khotib, Junaidi; Suharjono; Bintoro, Siprianus Ugroseno Yudho
- Abstract
Objectives: Among Chronic Myeloid Leukemia (CML) patients treated with Tyrosine Kinase Inhibitor (TKI-imatinib-nilotinib), some showed a suboptimal response. Based on pharmacokinetic studies, TKI trough level ( C m i n ∞ ${C}_{min}\hat{\infty }$) is associated with clinical outcomes, reflected by the BCR-ABL ratio. However, the interindividual pharmacokinetic variability of imatinib and nilotinib is found to be moderate–high. This study aims to analyze the relationship between TKI C m i n ∞ ${C}_{min}\hat{\infty }$ and BCL-ABL ratio in chronic-phase CML patients. Methods: Cross-sectional study to CML chronic-phase patients treated with imatinib 400 mg daily or nilotinib 400 or 800 mg daily for ≥12 months. The exclusion criteria were therapy discontinuation within 29 days (imatinib) or 8 days (nilotinib) before the sampling day. Blood samples were drawn 1 h before the next dose. Imatinib-nilotinib C m i n ∞ ${C}_{min}\hat{\infty }$ and BCR-ABL ratio were measured using HPLC and RT-qPCR. The relationship was analyzed using bivariate correlation Spearman's rho test. Results: Twenty-three imatinib and 11 nilotinib patients met the inclusion criteria. The mean imatinib and nilotinib C m i n ∞ ${C}_{min}\hat{\infty }$ were 1,065.46 ± 765.71 and 1,445 ± 1,010.35 ng/mL respectively. There were large interindividual variations in both groups (71.87% vs. 69.88%). Half of the patients in each group were found to reach C m i n ∞ ${C}_{min}\hat{\infty }$ target (≥1.000 ng/mL, imatinib; ≥800 ng/mL nilotinib), but only 12 (35,29%) of them result in BCR-ABL ratio ≤0.1%. C m i n ∞ ${C}_{min}\hat{\infty }$ imatinib was found to be significantly associated with BCR-ABL ratio. But, not with the nilotinib group. Conclusions: There were high interindividual variations of imatinib and nilotinib correlated with BCR-ABL ratio, but no correlation in nilotinib.
- Subjects
INDONESIA; HIGH performance liquid chromatography; PROTEIN-tyrosine kinases; STATISTICS; TRANSCRIPTION factors; DATA analysis; IMATINIB; PROTEIN-tyrosine kinase inhibitors; CHRONIC myeloid leukemia; CROSS-sectional method; DESCRIPTIVE statistics; NILOTINIB
- Publication
Journal of Basic & Clinical Physiology & Pharmacology, 2020, Vol 31, Issue 5, p1
- ISSN
0792-6855
- Publication type
Article
- DOI
10.1515/jbcpp-2019-0315