發(fā)布時間：2018-01-24 19:58

  本文關(guān)鍵詞： 非霍奇金淋巴瘤 甲氨蝶呤 血藥濃度 延遲排泄 肌酐清除率　出處：《河北醫(yī)科大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的:通過液相色譜串聯(lián)質(zhì)譜法(Liquid Chromatography Mass Spectrometry/Mass Spectrometry,LC-MS/MS)監(jiān)測非霍奇金淋巴瘤((Non-hodgkin lymphoma,NHL)患者在應(yīng)用大劑量甲氨蝶呤(High-dose methotrexate,HD-MTX)化療后血藥濃度,分析影響甲氨蝶呤(Methotrexate,MTX)血藥濃度的因素。研究甲氨蝶呤血藥濃度與其發(fā)生毒副反應(yīng)之間的相關(guān)性,為臨床實際工作中合理的應(yīng)用甲氨蝶呤并制定正確的解救治療方案提供依據(jù)。方法:對2016年1月至2016年12月期間38例于河北醫(yī)科大學第四醫(yī)院接受HD-MTX治療的成人及兒童NHL患者進行血藥濃度監(jiān)測,共計60例次,均為甲氨蝶呤44小時血藥濃度,其中男性38例次,女性22例次,年齡2歲至67歲。HD-MTX劑量為1-5g/m2,全部MTX藥量24h持續(xù)靜脈滴注。用藥當日及其后3天內(nèi)充分水化及堿化尿液,滴注甲氨蝶呤36 h后開始給予亞葉酸鈣(Calcium Folinate,CF)進行解救。初始解救劑量為15 mg/m 2,每6 h靜脈注射,具體解救劑量及次數(shù)根據(jù)甲氨蝶呤血藥濃度進行調(diào)整。采用LC-MS/MS法測定HD-MTX用藥后44h血清中MTX濃度,甲氨蝶呤濃度(C44 h)1.0μmol·L-1為排泄延遲組,甲氨蝶呤濃度(C44 h)≤1.0μmol·L-1為正常組,其中正常排泄組56例次,排泄延遲組4例次。1記錄患者年齡、體重指數(shù)(Body mass index,BMI)值、MTX給藥劑量,用獨立樣本t檢驗與多元線性回歸分析患者性別、年齡、BMI值、MTX給藥劑量與甲氨蝶呤濃度(C44 h)的相關(guān)性。2記錄治療后(44h)的血肌酐清除率(Creatinine clearance,Ccr),分析肌酐清除率(Ccr)與C44 h的相關(guān)性。3記錄HD-MTX化療后1-7天內(nèi)發(fā)生的骨髓抑制、肝功能異常、腎功能異常、胃腸道反應(yīng)、黏膜損害、皮疹、繼發(fā)感染等甲氨蝶呤毒副反應(yīng)。毒副反應(yīng)分級依據(jù)NCI-CTC毒性標準分級分為Ⅰ度至Ⅳ度。比較MTX正常排泄組與延遲排泄組毒副反應(yīng)發(fā)生率的相關(guān)性。結(jié)果:1單因素分析顯示甲氨蝶呤濃度(C44 h)與患者年齡、MTX給藥劑量、BMI值顯著相關(guān)(P0.05),與患者性別不相關(guān)。多元線性回歸分析顯示患者年齡、MTX給藥劑量是甲氨蝶呤濃度(C44 h)顯著獨立影響因素。2甲氨蝶呤濃度(C44 h)的排泄延遲率為6.67%,治療后44 h腎功能正常組與腎功能受損組的甲氨蝶呤濃度(C44 h)對比,差異均有統(tǒng)計學意義(P0.05)。3甲氨蝶呤毒副反應(yīng)發(fā)生率分別為骨髓抑制(68.3%)、胃腸道反應(yīng)(40.0%)、繼發(fā)感染(33.3%)、肝功能異常(33.3%)、黏膜損害(30.0%)、腎功能異常(20.0%)、皮疹(11.7%)。4延遲排泄組毒副反應(yīng)發(fā)生率高于正常組,其中腎毒性差異顯著(P0.05)而骨髓抑制、繼發(fā)感染、胃腸道反應(yīng)、肝功能異常、黏膜損害、皮疹的發(fā)生率兩組間無明顯差異(P0.05)。結(jié)論:1患者年齡、HD-MTX的給藥劑量是影響甲氨蝶呤濃度(C44 h)的顯著獨立影響因素。2腎功能正常的患者44 h的Ccr與甲氨蝶呤濃度(C44 h)存在著明顯相關(guān)性,提示腎功能仍是影響甲氨蝶呤排泄的主要因素之一。3甲氨蝶呤濃度(C44 h)監(jiān)測可以有效的預判斷MTX的排泄延遲,并為臨床正確應(yīng)用甲氨蝶呤以及制定亞葉酸鈣解救方案提供合理的依據(jù)。
[Abstract]:Objective: by liquid chromatography tandem mass spectrometry (Liquid Chromatography Mass Spectrometry/Mass Spectrometry, LC-MS/MS) monitoring of non Hodgkin's lymphoma (Non-hodgkin (lymphoma, NHL) patients were treated with high dose methotrexate (High-dose methotrexate, HD-MTX) blood concentration after chemotherapy, analysis of the effect of methotrexate (Methotrexate, MTX) factors of blood concentration of methotrexate. The correlation between plasma concentration and adverse reaction, for reasonable clinical application of methotrexate in practical work and provide the basis for the formulation of the correct rescue treatment. Methods: blood concentration monitoring in 38 cases during the period from January 2016 to December 2016 in the fourth hospital of Hebei Medical University in HD-MTX treated adults and children with NHL, a total of 60 cases. For 44 hours the blood concentration of methotrexate, including male 38 cases, female 22 cases, aged 2 to 67 years old.HD The dose of -MTX 1-5g/m2, all 24h MTX dose continuous intravenous drip medication. Adequate hydration and alkalization of urine within 3 days of the day and after infusion of methotrexate after 36 h was given calcium folinate (Calcium Folinate, CF) were rescued. The initial rescue dose of 15 mg/m 2, each of the 6 h intravenous injection, specific rescue dose and times were adjusted according to blood concentration of methotrexate. Measured by LC-MS/MS HD-MTX after administration of 44h in the serum concentration of MTX, concentration of methotrexate (C44 h) 1 mol - L-1 elimination delay group, methotrexate (C44 h) less than or equal to 1 mu mol L-1 in the normal group, the normal group of 56 cases. In 4 cases, delayed excretion of group.1 patients were recorded age, body mass index (Body mass, index, BMI) value, MTX dosage, regression analysis of the sex of the patient, with the independent sample t test and multiple linear age, BMI value, MTX dosage and methotrexate concentration (C44 h) correlation.2 Recorded after treatment (44h) blood creatinine clearance rate (Creatinine, clearance, Ccr), analysis of creatinine clearance rate (Ccr) and the inhibition of C44 correlation between H.3 records 1-7 days after HD-MTX chemotherapy in bone marrow, liver dysfunction, renal dysfunction, gastrointestinal reaction, mucosa damage, skin rash, toxicity secondary infection of methotrexate toxicity grading classification. According to the NCI-CTC toxicity criteria were divided into four degree. The degree to rate correlation between MTX group and normal group delayed excretion excretion toxicity. Results: 1 single factor analysis showed that the concentration of methotrexate (C44 h) and the age of patients, MTX dosage, BMI value was significantly correlated (P0.05), not related with gender. Multiple linear regression analysis showed that age, MTX dose methotrexate (C44 h) is a significant independent factors affecting the.2 concentration of methotrexate (C44 h) the delayed excretion rate of 6.67%, 44 h after treatment of renal function Group of methotrexate with impaired renal function group (C44 h) comparison, the differences were statistically significant (P0.05).3 methotrexate toxicity was myelosuppression (68.3%), gastrointestinal reactions (40%), secondary infection (33.3%), abnormal liver function (33.3%), (30%), mucosal damage abnormal renal function (20%), rash (11.7%).4 delayed excretion group adverse reaction rate is higher than the normal group, the renal toxicity was significantly different (P0.05) and bone marrow suppression, secondary infection, gastrointestinal reactions, abnormal liver function, mucosal injury, the incidence of rashes was no significant difference between the two groups (P0.05). Conclusion: 1 patients age, the dosage is HD-MTX (C44 h) effects of methotrexate concentration significantly independent determinants of.2 patients with normal renal function 44 h Ccr (C44 h) and methotrexate concentration has significant correlation, suggesting that renal function is the principal factor influencing the excretion of methotrexate A.3 methotrexate concentration (C44 h) monitoring can effectively predict the excretion delay of MTX, and provide a reasonable basis for the correct application of methotrexate and the formulation of calcium folate rescue plan.

【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R969

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