洛铂用于结直肠癌术中腹腔灌洗化疗的近期疗效分析

目的探讨洛铂用于结直肠癌术中腹腔灌洗化疗的安全性和可行性。 方法选取中国医学科学院肿瘤医院结直肠外科在2016年11月1日至2017年11月1日行结直肠癌根治术的患者160例,采用随机数余数分组法前瞻性随机分为洛铂灌洗化疗组（研究组）80例和无腹腔化疗组（对照组）80例,研究组术中行洛铂腹腔灌洗化疗,对照组不行腹腔化疗。分析两组术后肠道功能恢复、血液和肝肾功能毒性以及术后并发症等近期疗效的差异。 结果研究组和对照组术后总并发症发生率相似,分别为11.2%和12.5%（χ²=0.060,P=0.807）。两组患者术后肠道功能恢复状况、白细胞和血小板水平以及术后出现肝肾功能异常、消化道反应患者数量之间差异也均无统计学意义（均P>0.05）。 结论洛铂术中腹腔灌洗化疗并不增加结直肠癌患者毒副反应及术后并发症,具有良好的安全性和可行性。     

温热灌注化疗对结直肠癌患者免疫指标的影响

［摘要］　目的　评价腹腔内温热灌注化疗对结直肠癌术后外周血中免疫指标的影响。方法　将2010-01～2013-12以来手术切除的50例DukesB～C期的结直肠癌患者随机分成温热灌注化疗组及常温灌注化疗组。温热灌注化疗组在手术结束后用含氟尿嘧啶(5-FU)0.5 g/L、丝裂霉素(MMC)8 mg/L、奥沙利铂25 mg/L温热蒸馏水4 000 ml，温度控制在43～45 ℃，在腹腔灌洗1 h。常温灌注化疗组在手术结束后用含5-FU 0.5 g/L、丝裂霉素(MMC)8 mg/L、奥沙利铂25 mg/L常温蒸馏水4 000 ml，温度控制在25～30 ℃，在腹腔灌洗1 h。然后两组分别于术后1月、术后2月再次腹腔灌洗，两组患者均于治疗前、术中、术后1月、术后2月应用ELISA法测定两组患者外周血中IL-2、TNF-α水平。结果　与常温灌注化疗组相比，温热灌注化疗组的患者外周血中IL-2、TNF-α水平均明显升高，差异有统计学意义(P<0.05)。结论　腹腔内温热灌注化疗可促进Thl型免疫漂移，增强机体的抗肿瘤免疫功能，对预防和治疗结直肠癌腹腔内复发与肝转移有一定的作用。     

连续性静脉-静脉血液滤过对多器官功能衰竭患者头孢他啶药代动力学的影响研究

目的 研究连续性静脉-静脉血液滤过(CVVH)对应用头孢他啶(CAZ)的多器官功能衰竭(MOF)患者药代动力学影响。方法 根据患者内生肌酐清除率(Ccr)将2006年1月至2008年12月江苏省南通大学附属医院住院的18例MOF患者分为3组：Ccr＜15 mL/min(A组)、Ccr 15～50 mL/min(B组)、Ccr＞50 mL/min(C组),采用高效液相色谱法测定CAZ血药浓度,并计算药代动力学参数。结果 血清CAZ最低检测浓度为05 mg/L,在2～200 mg/L的浓度范围呈良好线性关系,回收率大于98%,日内和日间变异系数均小于10%;接受CVVH治疗的3组MOF患者血药峰浓度(Cmax)差异无统计学意义,与C组相比,A组与B组血药谷浓度(Cmin)增高［(36.01±9.36)mg/L,(19.81±2.36)mg/L对(8.33±3.75)mg/L,P<0.05］,总体清除率(ClT)降低［(20.98±6.02)mL/min,(33.33±9.08)mL/min对(97.28±14.35)mL/min,P<0.05］,消除半衰期(t1/2)［(8.49±1.41)h,(4.46±0.64)h对(2.13±0.34)h,P<0.05］和药物平均滞留时间(MRT)［(11.99±1.87)h,(5.65±0.35)h对(2.96±0.44)h,P<0.05)］延长,且与患者自身肾功能密切相关;A组稳态分布容积(Vss)较C组减小［(12.55±2.42)L比(17.67±2.31)L,P<0.05］。t1/2与Ccr呈负相关性,ClT与Ccr呈正相关性。结论 CVVH可增加MOF患者对CAZ的体外清除,临床用药时应考虑多种影响因素,并监测血药浓度以提高疗效、减少副反应。     

洛铂与草酸铂在联合化疗方案中毒副作用的比较

目的:比较洛铂、草酸铂在氟尿嘧啶、四氢叶酸钙联合化疗方案中的毒副作用.方法:将2006-2007年52例结、直肠癌术后患者随机分为两组,洛铂联合化疗组26例,共85个疗程,草酸铂联合化疗组26例,共73个疗程.化疗方案为洛铂50 mg/m2或草酸铂85 mg/m2,静脉滴注2 h以上,第1天;四氢叶酸钙200 mg/m2静脉滴注2 h以上,第1天和第2天;氟尿嘧啶400mg/m2静脉推注,然后600mg/m2持续静脉输注22 h以上,第1天和第2天;每2周重复.结果:毒副作用以骨髓抑制及胃肠道反应为主.洛铂组和草酸铂组患者白细胞减少Ⅰ-Ⅱ级分别占60.0%,50.7%;血小板减少Ⅰ-Ⅱ级占66.7%,21.3%;胃肠道反应恶心占16.7%,37.3%;发生呕吐占3.3%,6.7%;洛铂组患者白细胞和血小板减少Ⅲ级分别占6.7%,10.0%,周围神经症状Ⅰ级占5.9%;草酸铂组白细胞减少Ⅲ-Ⅳ级占41.3%,周围神经症状Ⅰ-Ⅱ级占42.7%,Ⅲ-Ⅳ级占9.3%.结论:洛铂、草酸铂分别与氟尿嘧啶和四氢叶酸钙联合使用均为安全的化疗方案.洛铂组对骨髓的抑制主要表现在血小板减少,而草酸铂组主要表现在白细胞减少.洛铂组的胃肠道反应及神经毒性较草酸铂组轻.     

腹腔内注射贝伐珠单抗治疗结直肠癌患者恶性腹腔积液的疗效和安全性评价

目的探讨腹腔内注射贝伐珠单抗治疗恶性腹腔积液的近期疗效及安全性; 方法收集46例桂林医学院附属医院胃肠外科2010年3月至2014年5月伴有难以控制的恶性腹腔积液的晚期结直肠癌患者。检测其腹腔积液中VEGF含量;并利用单因素生存分析对比两组患者的预后。 结果对照组的血清VEGF平均值为（671.8±499.15）pg/mL,与治疗组［平均值为（665.19.19±499.15）pg/mL］相比差异无统计学意义。治疗组中,治疗前腹腔积液VEGF量的平均值为（1 225.11±609.71）pg/mL,无穿刺中位生存时间为6个月（1~21个月）。与对照组相比,治疗组的穿刺引流时间明显延长（t值=6.328,P<0.05）。治疗后,腹腔积液的VEGF量（317.69±172.14）pg/mL,与治疗前相比差异存在统计学意义。治疗后的血清VEGF平均值为（170.61±115.92）pg/mL,与治疗前差异具有统计学意义。在生存分析中,治疗组的预后明显好于对照组（P<0.05）。 结论对于一部分合适的患者,腹腔内注射贝伐珠单抗对于恶性腹腔积液的治疗可能是一种有效地、安全的治疗手段。     

机器人结直肠癌根治术的初步应用体会

目的探讨达芬奇机器人手术系统应用于结直肠癌手术的初步体会。 方法回顾性收集吉林省肿瘤医院腹部肿瘤科2014年10月至2016年5月的63例结直肠癌行机器人手术患者临床数据,进行整理分析。 结果63例手术均顺利完成,无一例中转开腹,无术后并发症,机器人安装时间为（15.24±5.69）min,手术时间为（176.43±59.39）min,术中出血量（28.65±22.36）mL,清扫淋巴结数（14.47±5.67）枚,术后排气时间（51.43±12.96）h,术后住院日（8.22±1.52）d。 结论达芬奇机器人手术系统应用于结直肠癌的手术治疗安全可行,手术效果好,术后恢复快,适合临床应用。     

国产硫酸氢氯吡格雷在中国健康受试者体内药代动力学和生物等效性研究

目的:研究硫酸氢氯吡格雷在中国健康受试者体内的药代动力学特性并评价其生物等效性.方法:23例中国男性健康受试者随机交叉单剂量口服泰嘉(国产硫酸氢氯比格雷,75mg/片,深圳信立泰药业股份有限公司生产)和波立维(原研厂硫酸氢氯比格雷,75mg/片,杭州赛诺菲-安万特制药有限公司)各150 mg后,采用高效液相色谱-串联质谱法测定血浆中氯吡格雷和氯吡格雷酸的浓度,并进行药代动力学和生物等效性研究.结果:口服泰嘉受试制剂者和波立维参比制剂者血浆中氯吡格雷血药达峰浓度(Cmax)分别为(3.07±3.63)ng/ml和(2.67±2.35)ng/ml;消除半衰期(t1/2)分别为(6.57±3.18)h和(6.96±3.92)h;药物浓度-时间曲线下面积(AUC)0-t分别为(4.75±4.68)ng.h/ml和(4.60±4.20)ng·h/ml.氯吡格雷酸的cmax分别为(6 724±1 899)ng/ml和(6 262±1 968)ng/ml;t1/2分别为(8.77±1.20)h和(10.11±8.99)h;AUC0-t分别为(20 702±5 579)ng·h/ml和(19 817+4 232)ng·h/ml.口服泰嘉受试制剂者相比波立维参比制剂者氯吡格雷和氯吡格雷酸的相对生物利用度分别为(112.8±42.4)%和(107,4±31,6)%.结论:AUC0-t,AUC--∞和cmax经对数转换后,应用方差分析法、双单侧t检验及90%置信区间判断,两种制剂具有生物等效性.     

含洛铂联合化疗方案治疗晚期消化道恶性肿瘤Meta分析

目的 探讨含洛铂联合化疗方案治疗常见晚期消化道恶性肿瘤的近期疗效及不良反应.方法 收集2005年来国内关于含洛铂化疗方案治疗晚期食管及胃肠恶性肿瘤的随机对照研究,并用Meta分析方法进行综合分析.结果 纳入文献6篇,其中食管癌3篇、胃癌1篇、结直肠癌2篇,含洛铂联合化疗方案与含顺铂/奥沙利铂联合化疗方案治疗食管癌、胃癌及结直肠癌相比,在有效率及临床受益率方面差异无统计学意义,在血液毒性、消化道反应、肝肾毒性、外周神经毒性等不良反应,尤其是血小板下降方面的差异无统计学意义.结论 含洛铂联合化疗方案可用于治疗晚期食管、胃及结直肠癌,尤其是对于不能耐受顺铂以及年老体弱患者,可以作为一个较好的替代选择.     

榄香烯乳联合洛铂腹腔热灌注治疗中晚期结直肠癌恶性腹水的临床研究

目的探讨榄香烯乳联合化疗药物洛铂腹腔热灌注对中晚期恶性结直肠癌腹水的临床疗效。方法对2017年1月至2019年12月,广州医科大学附属肿瘤医院诊断为中晚期大肠癌并伴恶性腹水的患者共40例,按照入组条件,遵循抛硬币法分为治疗组(20例),对照组(20例),对照组予单药洛铂(50 mg),治疗组予洛铂(50 mg)加中药榄香烯乳(400 mg/m 2)行腹腔热灌注治疗。对两组治疗前后4周的疗效进行比较。采用WHO腹水治疗疗效评估标准,比较两组的客观缓解率,用Karnofsky(KPS)体能评分标准对病人的体能改善进行评价,并对病人消化道不良反应发生率进行评价。结果40例患者全部完成治疗。治疗组的客观缓解率为80%,显著高于对照组的40%(P<0.05)。化疗后4周,治疗组的KPS评分、白细胞、血红蛋白、血小板均显著优于对照组(P<0.05)。组内比较,治疗组血红蛋白化疗前后的变化有统计学差异,对照组白细胞、血小板、血红蛋白化疗前后均有统计学差异。结论中药榄香烯联合洛铂腹腔热灌注可明显改善腹水病人的体力状况,减轻单用化疗药物热灌注的毒副作用,疗效优于单用洛铂,消化道不良反应发生率低。     

血清CEA水平＞100ng/mL结直肠癌患者临床特点分析

目的 探讨癌胚抗原（CEA）＞ 100 ng/mL结直肠癌患者的临床特点.方法 收集血清CEA水平＞100ng/mL的结直肠癌患者临床资料,并选取CEA水平20～100 ng/mL患者做对照组,进行回顾性分析.结果 两组镜下病理,CEA＞ 100 ng/mL组恶性程度高;CEA＞ 100 ng/mL组出现转移的可能性较大;Dukes分期,CEA＞ 100 ng/mL组分期较晚.结论 血清CEA水平的高表达（＞100 ng/mL）并不能代表分化程度差,浸润程度高,有淋巴结转移,而能预示病理类型较差,远处转移的可能性明显升高.     

Infected hepatic cyst

We describe an unusual case involving an infected hepatic cyst. An 88-year-old woman presented with acute onset of right upper quadrant abdominal pain, mild left lower abdominal pain, diarrhea, and fever. On admission, computed tomography revealed multiple hepatic cysts including an 8-cm cyst located in the left medial segment of the liver, which demonstrated a thickened wall enhanced with contrast media. Ultrasonography showed an 8-cm hypoechoic lesion which differed in appearance from the other, anechoic hepatic cysts. The serum concentration of C-reactive protein was 29.8 mg/dL; white blood cell count, 12,800/microL; CA19-9, 96 U/mL; and CEA, 2.2 ng/mL. Diagnosis of infected hepatic cyst was made by percutaneous transhepatic drainage of the cyst. Milky fluid was obtained and the patient's right upper quadrant abdominal pain resolved after drainage. The cyst fluid CA19-9 concentration was 18,000 U/mL. Cytology of the cyst fluid was negative. Serum CA19-9 (41 U/mL) and CEA (1.8 ng/mL) concentrations were improved 1 week after drainage. Escherichia coli was cultured from the drainage fluid. The patient was discharged 27 days after admission. Percutaneous transhepatic drainage is effective in the treatment of infected hepatic cysts.     

A rapid and simple CYP2D6 genotyping assay--case study with the analgetic tramadol

There is substantial evidence for a causal relationship between genetic variability of the CYP2D6 gene and changes in the pharmacokinetics of drugs. Therefore, knowledge of single-nucleotide polymorphisms (SNPs) prior to drug administration is highly desired for assisting in the development of individualized pharmacotherapy. We therefore developed a robust assay that detects common CYP2D6 alleles within 60 minutes of blood withdrawal and links carriers of the variant CYP2D6∗3 and ∗4 alleles to the pharmacokinetics of tramadol. This new genotyping assay employs fluorescence resonance energy transfer (FRET) analysis, which permits parallel identification of the CYP2D6∗3 and CYP2D6∗4 alleles within 60 minutes of blood withdrawal. We determined the genotypes of 100 healthy unrelated individuals and studied the pharmacokinetics of tramadol in 24 CYP2D6 genotyped healthy subjects. The total allelic frequencies of homozygote carriers were 0.015 and 0.25 for the CYP2D6∗3 and ∗4 alleles, respectively, and the plasma area under the curve (AUC) was 84% above those of extensive metabolizers (homozygous EM group): 3,941.2 ng/mL · h (95% confidence interval [CI], 2,928.9 ng/mL · h to 4,953.5 ng/mL · h) versus 2,142.6 ng/mL · h (95% CI, 1,829.6 ng/mL · h to 2,455.7 ng/mL · h). Likewise, the AUC for the O-desmethyl-tramadol metabolite (M1) was significantly reduced in poor metabolizers (PMs): 300.2 ng/mL · h (95% CI, 260.3 ng/mL · h to 340.0 ng/mL · h) versus 842,6 ng/mL · h (95% CI, 715.1 ng/mL · h to 970.0 ng/mL · h). We observed a statistically significant correlation between plasma tramadol AUC and production of the O-desmethyl metabolite in CYP2D6 genotyped healthy volunteers. Our assay can be used reliably in clinical pharmacology studies and may be used for dose adjustment.     

The effect of a high-fat breakfast on the pharmacokinetics of moxidectin in healthy male subjects: a randomized phase I trial

The objective of this study was to assess the effect of a high-fat meal on the pharmacokinetics of moxidectin. Healthy male subjects were randomized to receive single oral 8 mg doses of moxidectin after an overnight fast or high-fat breakfast. In fasted subjects (N = 27), mean [SD] parameters were C(max): 58.9 [12.5] ng/mL; t(max): 3.7 [1.5] h; area under concentration-time curve (AUC): 3,387 [1,328] ng/h/mL; Vλ(z)/F: 2,829 [1,267] L; CL/F: 2.76 [1.28] L/h; and t(1/2): 784 [347] h. Compared with fasted subjects, fed subjects (N = 27) exhibited a 34% increase in C(max), delay in t(max) to 5.3 [2.1] h, 44% increase in AUC, 40% decrease in Vλ(z)/F, and a 35% decrease in CL/F. There was no significant change in t(1/2). The changes are consistent with an increase in moxidectin bioavailability following administration with food. There were no clinically relevant changes in vital signs, laboratory tests, or electrocardiograms.     

Prognostic significance of the serum thymidine phosphorylase levels in venous blood drainage specimens in patients with colorectal cancer

BACKGROUND/AIMS: We investigated whether the serum Thymidine phosphorylase (TP) levels in venous blood drainage specimens were associated with the prognosis and risk of liver metastasis in patients with resectable colorectal cancer. METHODOLOGY: From 88 patients with colorectal cancer, specimens of venous blood drainage were obtained during operation. The serum TP levels were measured by a highly sensitive Enzyme-Linked Immunosorbent Assay (ELISA) method. RESULTS: Subsequently, 88 patients were divided into two groups based on the levels of TP. The dividing line was determined to be 55ng/mL. The TP-high group (> 55ng/mL) had a significantly shorter overall survival than the TP-low group (< 55ng/mL). A multivariate analysis indicated that the serum TP level in venous blood drainage specimens to be a better prognostic factor independent of the traditional pathologic parameters. The serum TP levels of 3 patients with metachronous liver metastasis were high (> 55ng/mL). CONCLUSIONS: These findings suggest that the serum TP levels in venous blood drainage specimens reflect the prognosis of patients with colorectal cancer undergoing curative resection, particularly the risk of liver metastasis.     

An open-label, randomized, cross-over bioequivalence study of lafutidine 10 mg under fasting condition

AIM: To assess the relative bioavailability and pharmacokinetic properties of two formulations (test and reference) of Lafutidine 10 mg.METHODS: The study was performed as an open label, randomized, two-way, two-period, two-treatment, single dose cross-over bioequivalence study, under non-fed condition to compare the pharmacokinetic profiles of the lafutidine formulation manufactured by Emcure Pharmaceuticals Ltd., India using an indigenously developed active pharmaceutical ingredient (API) and the commercially available Stogra^® formulation, of UCB Japan Co., Ltd., Japan. The two treatments were separated by a wash-out period of 5 d. After an overnight fasting period of 10 h, the subjects were administered either the test or the reference medication as per the randomization schedule. Blood samples were collected at intervals up to 24 h, as per the approved protocol. Concentrations of lafutidine in plasma were analyzed by a validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) method, and a non-compartmental model was used for pharmacokinetic analysis. The pharmacokinetic parameters were subjected to a 4-way ANOVA accounting for sequence, subjects, period and treatment. Statistical significance was evaluated at 95% confidence level (P ≥ 0.05).RESULTS: The mean (± SD) values of the pharmacokinetic parameters (test vs reference) were C_max (265.15 ± 49.84 ng/mL vs 246.79 ± 29.30 ng/mL, P < 0.05), Area under the curve (AUC)_(0-t) (1033.13 ± 298.74 ng.h/mL vs 952.93 ± 244.07 ng.h/mL, P < 0.05), AUC_(0-∞) (1047.61 ± 301.22 ng.h/mL vs 964.21 ± 246.45 ng.h/mL, P < 0.05), and t_½(1.92 ± 0.94 h vs 2.05 ± 1.01 h, P < 0.05). The 90% confidence intervals (CI) for the test/reference ratio of mean C_max, AUC_(0-t), and AUC_(0-∞) were within the acceptable range of 80.00 to 125.00. The mean times (± SD) to attain maximal plasma concentration (t_max) of lafutidine were 0.95 ± 0.24 h vs 1.01 ± 0.29 h (P < 0.05) for the test and the reference formulations respectively. Both the formulations were well tolerated.CONCLUSION: In summary, this study has demonstrated the bioequivalence of the two formulations of lafutidine 10 mg. Hence it can be concluded that the two formulations can be used interchangeably in clinical settings.     

Induction of anti-recombinant human granulocyte-macrophage colony- stimulating factor (Escherichia coli-derived) antibodies and clinical effects in nonimmunocompromised patients

The pharmacokinetics of recombinant human granulocyte-macrophage colony- stimulating factor (rhGM-CSF), induction of anti-GM-CSF antibodies, and clinical effects related to the induction of the antibodies were analyzed in patients with metastatic colorectal carcinoma (CRC) who were not on chemotherapy (n = 20, nonimmunocompromised patients). rhGM- CSF (250 micrograms/m2/d; Escherichia coli-derived) was administered subcutaneously for 10 days every month for 4 months. Eight patients with multiple myeloma (MM) on intensive chemotherapy followed by rhGM- CSF treatment were also included (immunocompromised patients). After a single injection of GM-CSF at the first cycle in CRC patients, the maximum calculated concentration (Cmax) was 5.24 +/- 0.56 ng/mL; the half life (T1/2) was 2.91 +/- 0.8 hours; and the area under the concentration curve (AUC) was 30.86 +/- 6.03 hours x ng/mL (mean +/- SE). No anti-GM-CSF antibodies were detected. During the subsequent cycles, 95% of the CRC patients developed anti-GM-CSF IgG antibodies, which significantly altered the pharmacokinetics of rhGM-CSF at the third and fourth cycles with decreased Cmax (2.87 +/- 0.57 ng/mL; P < .05), T1/2 (1.57 +/- 0.2 hours; P < .05), and AUC (14.90 +/- 4.10 hours x ng/mL; P < .005). The presence of anti-GM-CSF antibodies significantly reduced the GM-CSF-induced enhancement of granulocytes, and there was a clear tendency for a decreased increment of monocytes. Antibodies diminished systemic side effects of rhGM-CSF. Only 1 of 8 MM patients showed a very low anti-GM-CSF antibody titer after GM-CSF therapy, as shown by enzyme-linked immunosorbent assay and Western blot. Therefore, in nonimmunocompromised patients, exogenous nonglycosylated GM-CSF induced an anti-GM-CSF IgG antibody response in practically all patients, which seemed to be of clinical significance. In immunocompromised patients, virtually no significant antibody response was shown.     

Systemic Effect of Endoscopic Ultrasonography-Guided Pancreatic Cyst Ablation with Ethanol and Paclitaxel

Background

Endoscopic ultrasonography (EUS)-guided pancreatic cyst ablation is a minimally invasive treatment modality. Local injection of ablative agents may rarely cause systemic effects in patients.

Aims

This study aimed to evaluate the systemic effect of ablative agents by analyzing the plasma drug concentration.

Methods

Ten patients with pancreatic cysts were enrolled. Cyst ablation was performed by 99 % ethanol lavage (2.5–70 mL) and paclitaxel (Genexol-polymeric micelle, 6.0–24.0) injection. Blood samples were collected at 0, 2, 4, 7 and 24 h. Plasma paclitaxel concentration was analyzed by a liquid chromatography-tandem mass spectrometry with the lowest limit of quantitation of 0.1 ng/mL. Procedure-related complications were closely monitored.

Results

Pancreatic cysts were located at the head in two, body in seven and tail in one patient. Eight cysts were septated. Median diameter and original volume were 39.5 mm (range 2.7–21.8) and 14.79 mL (3.42–343.30). Median cyst fluid CEA and amylase values were 17.10 ng/mL (0.5–14127.5) and 73.50 U/L (3.1–91,590). Peak plasma paclitaxel concentration values were observed between 2 and 7 h, ranging from 0.45 to 14.73 ng/mL. The highest concentration (17.10 ng/mL at 0 h) was observed in a patient who had intracystic bleeding. Mild abdominal pain occurred in five patients and vomiting in one patient during the first 48-h monitoring.

Conclusion

Plasma paclitaxel concentration after EUS-guided pancreatic cyst ablation was nearly as low as the undetectable value and rarely caused systemic side-effect.     

健康受试者他克莫司代谢与CYP3A5基因多态性的相关性

目的观察细胞色素P450 3A5（CYP3A5）基因多态性对他克莫司代谢的影响,分析他克莫司在不同个体间吸收、代谢差异的基因背景,以建立个体化用药的药物代谢遗传学监控体系。方法选择23例健康男性,单剂量口服他克莫司5mg,测定服药后不同时间血药浓度,并计算药代动力学参数。RT-PCR方法检测CYP3A5＊3的多态性,并比较不同基因型之间他克莫司药代动力学参数的差异。结果CYP3A5＊3基因6986A〉G中,＊1／＊1型为1例,＊1／＊3型为12例,＊3／＊3型为10例。＊1／＊1型和＊1／＊3型患者的他克莫司Cmax、AUC0-t、AUC0-∞明显低于＊3／＊3型患者（P均〈0．05）,＊1／＊1型纯合子的药代动力学参数略低于＊1／＊3型杂合子,但无统计学意义。结论CYP3A5＊3基因多态性与他克莫司的代谢密切相关,分析CYP3A5＊3基因多态性可以为器官移植患者个体化用药提供更可靠的依据。