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Development of a dried blood spot sampling method towards therapeutic monitoring of radotinib in the treatment of chronic myeloid leukaemia
Author(s) -
Lee Jihyun,
Jung Su Young,
Choi MiYeon,
Park Jisu,
Park Sukyoung,
Lim SeonAh,
Cho Kyung Hee,
Oh Soo Yeon,
Ha Jungeun,
Kim DongWook,
Lee Jangik
Publication year - 2020
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.13124
Subject(s) - dried blood spot , blood sampling , therapeutic drug monitoring , chromatography , sampling (signal processing) , pharmacokinetics , linear regression , regression analysis , chronic myeloid leukaemia , medicine , chemistry , statistics , pharmacology , mathematics , computer science , filter (signal processing) , computer vision
What is known and objective Dried blood spot (DBS) sampling is a minimally invasive method of blood sampling that enables monitoring of drug concentrations to be more convenient. This study aimed at developing a DBS sampling method for an accurate and precise prediction of radotinib plasma concentrations ( C p ) in patients with chronic myeloid leukaemia (CML). Methods Dried blood spot and venous blood samples were simultaneously collected from fifty CML patients who had been receiving radotinib for at least a week. Radotinib concentrations were measured using a high‐performance liquid chromatographic method with tandem mass spectrometric detection. Unmeasured C p was predicted directly based on a Deming regression between DBS concentrations ( C DBS ) and C p . Unmeasured C p was also predicted from C DBS corrected by each patient's haematocrit (Hct). Both prediction methods were evaluated for their accuracy and precision using Deming regression and Bland‐Altman analysis. Results and discussion The Deming regression equation between C DBS and C p was obtained as follows: C p = 1.34∙ C DBS + 4.26 ( r 2 = .97). C p was directly predictable using C p,pred1 = 1.34∙ C DBS + 4.26. With Hct correction, C p was alternatively predictable using C p,pred2 = C DBS / (1–Hct + Hct 2 ). The slopes of Deming regression line between predicted and measured C p were 0.99 and 1.02 for the direct and Hct‐corrected method, respectively. The mean biases (accuracy) were −0.44% and 1.6% with the 95% limits of agreement (precision) of −22.4% to 21.5% and −20.5% to 23.7%, respectively. More than 93% of predicted and measured C p pairs had their differences within 20% of the mean of each pair in both methods. What is new and conclusions Radotinib C DBS are highly correlated with radotinib C p. Radotinib C p can be accurately and precisely predicted from C DBS using direct or Hct‐corrected prediction methods. Both appear to be appropriate for the therapeutic monitoring of radotinib in patients with CML.