OBJECTIVE:To investigate the value of population pharmacokinetics (PPK) in individualized rescue for an acute lymphoblastic leukemia (ALL) child with severe methotrexate (MTX) excretion delay, and to provide reference for clinical pharmaceutical care. METHODS: Clinical pharmacists participated in clinical rescue for an ALL child with severe MTX excretion delay. The child suffered from severe MTX excretion delay after high dose MTX (HD-MTX) chemotherapy. Clinical pharmacists used PPK model and Bayesian feedback method to predict plasma concentration of MTX. According to measured results and predicted results, rescue dose of calcium folinate (CF) was adjusted to 160 mg/time on the 6th, 7th day after admission for intravenous dripping 1 h, based on initial rescue dose (15 mg/m2,ivgtt,q6 h) of CF; on the 8th day, CF rescue dose was adjusted to 42 mg/time; on the 9th, 10th day, CF rescue dose was adjusted to 21 mg/time; on the 11th-16th day, CF recue dose was adjusted to 10.5 mg/time; 4 times a day. Considering the mild impairment of renal function, clinical pharmacists proposed to discontinue omeprazole and use Cimetidine injection 0.2 g, ivgtt, qd, for protecting stomach, and decrease the dose of Cefazidime for injection to 0.4 g, ivgtt, tid; strengthen hydration, alkalization and oral mucosa care. RESULTS: Physicians adopted to the suggestions of clinical pharmacists. The difference between predicted value of plasma concentration of MTX and measured value was less than ±0.32 μmol/L. The predictive results showed favorable accuracy. After the adjustment of CF rescue plan under the guidance of PPK model, plasma concentration of MTX decreased to 0.13 μmol/L. The child completed chemotherapy successfully and discharged from the hospital on the 18th day after admission. CONCLUSIONS: PPK theory can provide reference for clinical rescue in ALL patients with severe MTX excretion delay, and can be used as one of breakthrough points for clinical pharmacists to carry out pharmaceutical care. When the patient suffered from severe MTX excretion delay, clinical pharmacists should fully grasp the influential factors of MTX excretion, and consider the physiological and pathological conditions of the patients, drug combination and plasma concentration, so as to ensure the timely and effective rescue.
关键词
甲氨蝶呤亚叶酸钙排泄延迟解救群体药动学贝叶斯反馈法药学监护
Keywords
MethotrexateCalcium folinateExcretion delayRescuePopulation pharmacokineticsBayesian feedback methodPharmaceutical care
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Related Author
WU Yanyan
WANG Can
YANG Xinwei
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LI Chenlu
PAN Hongming
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Related Institution
Dept. of Pharmacy, Second Affiliated Hospital, Army Medical University
Dept. of Pharmacy, Chongqing Health Center for Women and Children/Women and Children’s Hospital of Chongqing Medical University