Budi Suprapti and Mareta Rindang Andarsari and Pharmasinta Putri Hapsari and Junaidi Khotib and Suharjono and Siprianus Ugroseno Yudho Bintoro (2020) 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. Journal of Basic and Clinical Physiology and Pharmacology, 31 (5). pp. 1-6. ISSN 2191-0286

	Text (PEER REVIEW) Validasi C-04.pdf Download (1MB)
	Text (SIMILARITY) C-04 Result.pdf Download (2MB)
	Text (FULLTEXT) Artikel C-04.pdf Download (3MB)
	Text (KORESPONDENSI) C-04 Koresponden.pdf Download (2MB)

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∞min) 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∞min 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∞min 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∞min 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∞min 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∞min 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.

Actions (login required)

View Item