不同剂型异烟肼、利福平血药浓度监测

doi:10.3969/j.issn.1004-583X.2024.11.005

摘要/Abstract

摘要：

目的分析不同剂型异烟肼(isoniazid, INH)、利福平(rifampicin, RFP)的血药浓度。方法纳入2022年7月20日至2022年11月30日在昆明市第三人民医院结核二科住院的活动性结核病患者123例。将患者随机分为注射组( $n$ =64)和口服组( $n$ =59),两组均服用乙胺丁醇和吡嗪酰胺,在此基础上,给予注射组RFP注射液和INH注射液,给予口服组RFP胶囊和INH片。于治疗第7天用药2 h、24 h后采集患者血液标本,采用高效液相色谱法检测两组INH、RFP的血药浓度。结果两组年龄、性别、体质量指数、治疗史、结核菌培养、病灶差异均无统计学意义(P>0.05)。治疗第7天用药2 h后注射组RFP血药浓度和达到目标浓度的占比均高于口服组(P<0.05),注射组RFP血药浓度<8 mg/L、8~24 mg/L的占比均小于口服组,血药浓度>24 mg/L的占比大于口服组,差异均有统计学意义(P<0.05)。多元线性回归模型分析显示,年龄是INH血药浓度的影响因素,年龄越大血药浓度越低,模型检验 $F$ =7.774, P=0.006。结论 RFP注射液血药浓度明显高于口服RFP胶囊,临床对于重症或口服治疗胃肠反应大的患者可优先考虑使用RFP注射剂型,以进一步提高临床疗效。建议INH按体质量给药以提高其血药浓度,并加强其血药浓度的监测。

关键词: 结核, 利福平, 异烟肼, 不同剂型, 血药浓度

Abstract:

Objective To measure blood concentrations of isoniazid (INH) and rifampicin (RFP) in different dosage forms. Methods From July 20, 2022 to November 30, 2022, 123 patients with active tuberculosis hospitalized in the Second Department of Tuberculosis of Kunming Third People's Hospital were included. They were randomly divided into injection group ( $n$ =64) and oral group ( $n$ =59). Both groups were given ethambutol and pyrazinamide. Additionally, the injection group was given RFP injection and INH injection, and the oral group was given RFP capsules and INH tablets. On the 7th day of treatment, blood samples were collected 2 hours and 24 hours after treatment, and the blood concentrations of INH and RFP in the two groups were detected by high performance liquid chromatography.Results There were no significant differences in age, sex, body mass index, treatment history, tuberculosis culture and lesion between the two groups (P>0.05). After 2 hours of medication on the 7th day of treatment, blood concentration of RFP and the proportion of patients with a targeted blood concentration of RFP were significantly higher in the injection group than those of the oral group (P<0.05). The proportions of patients with blood concentration of RFP<8 mg/L and 8-24 mg/L in the injection group was significantly lower than that of the oral group, and the proportion of patients with blood concentration of RFP>24 mg/L was significantly higher than that of the oral group (P<0.05). Multivariate linear regression model analysis showed that age was the influencing factor of blood concentration of INH. The older the age, the lower the blood concentration of INH ( $F$ =7.774, P=0.006).Conclusion The blood concentration of RFP injections is significantly higher than that of oral RFP capsules. For patients with severe or oral treatment of gastrointestinal reactions, RFP injections can be given priority to improve the clinical efficacy. INH is recommended to be given according to body weight, aiming to increase the blood concentration and strengthen the blood concentration monitoring.

Key words: tuberculosis, rifampicin, isoniazid, different dosage forms, blood concentration

中图分类号:

汪林, 万荣, 刘莎, 刘蕾, 何静, 唐理斌, 李明武. 不同剂型异烟肼、利福平血药浓度监测[J]. 临床荟萃, 2024, 39(11): 989-992.

Wang Lin, Wan Rong, Liu Sha, Liu lei, He Jing, Tang Libin, Li Mingwu. Monitoring of blood concentrations of isoniazid and rifampicin in different dosage forms[J]. Clinical Focus, 2024, 39(11): 989-992.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2024.11.005

https://huicui.hebmu.edu.cn/CN/Y2024/V39/I11/989

图/表 7

表1 两组一般资料比较

Tab.1 General information between groups

组别	例数	年龄 (岁)	BMI (kg/m²)	性别[例(%)]		治疗史[例(%)]		结核菌培养[例(%)]		病灶[例(%)]
组别	例数	年龄 (岁)	BMI (kg/m²)	男	女	初治	复治	阳性	阴性	空洞	浸润	粟粒
口服组	59	42.7±13.5	23.0±3.6	35(59.3)	24(40.7)	48(81.4)	11(18.6)	22(37.3)	37(62.7)	7(11.9)	49(83.1)	3(5.0)
注射组	64	43.2±13.3	22.5±1.8	41(64.1)	23(35.9)	55(85.9)	9(14.1)	20(31.3)	44(68.7)	9(14.1)	49(76.6)	6(9.3)
$t$ /χ²值		0.184	-0.980	2.246		0.526	0.234	0.339	0.587	0.324	1.097	0.790
P值		0.854	0.329	0.134		0.468	0.629	0.561	0.444	0.569	0.295	0.374

表1 两组一般资料比较

Tab.1 General information between groups

组别	例数	年龄 (岁)	BMI (kg/m²)	性别[例(%)]		治疗史[例(%)]		结核菌培养[例(%)]		病灶[例(%)]
组别	例数	年龄 (岁)	BMI (kg/m²)	男	女	初治	复治	阳性	阴性	空洞	浸润	粟粒
口服组	59	42.7±13.5	23.0±3.6	35(59.3)	24(40.7)	48(81.4)	11(18.6)	22(37.3)	37(62.7)	7(11.9)	49(83.1)	3(5.0)
注射组	64	43.2±13.3	22.5±1.8	41(64.1)	23(35.9)	55(85.9)	9(14.1)	20(31.3)	44(68.7)	9(14.1)	49(76.6)	6(9.3)
$t$ /χ²值		0.184	-0.980	2.246		0.526	0.234	0.339	0.587	0.324	1.097	0.790
P值		0.854	0.329	0.134		0.468	0.629	0.561	0.444	0.569	0.295	0.374

表2 两组治疗第7天用药2 h、24 h后INH、RFP血药浓度比较

Tab.2 The blood concentrations of INH and RFP at 2 hours and 24 hours of medication on the 7th day of treatment between groups

组别	例数	用药2 h后		用药24 h后
组别	例数	INH(mg/L)	RFP(mg/L)	INH(mg/L)	RFP(mg/L)
口服组	59	2.18(1.47, 3.77)	21.34(5.97, 38.64)	1.40(0.86, 3.17)	3.07(1.85, 9.49)
注射组	64	2.21(1.10, 4.52)	47.95(33.49, 80.16)	1.28(0.93, 2.51)	5.26(1.89, 10.84)
$Z$ 值		-0.013	-5.501	-0.856	-0.330
P值		0.990	<0.001	0.392	0.741

表2 两组治疗第7天用药2 h、24 h后INH、RFP血药浓度比较

Tab.2 The blood concentrations of INH and RFP at 2 hours and 24 hours of medication on the 7th day of treatment between groups

组别	例数	用药2 h后		用药24 h后
组别	例数	INH(mg/L)	RFP(mg/L)	INH(mg/L)	RFP(mg/L)
口服组	59	2.18(1.47, 3.77)	21.34(5.97, 38.64)	1.40(0.86, 3.17)	3.07(1.85, 9.49)
注射组	64	2.21(1.10, 4.52)	47.95(33.49, 80.16)	1.28(0.93, 2.51)	5.26(1.89, 10.84)
$Z$ 值		-0.013	-5.501	-0.856	-0.330
P值		0.990	<0.001	0.392	0.741

表3 治疗第7天服药2 h后不同剂型INH、RFP血药浓度占比比较

Tab.3 The blood concentrations of INH and RFP in different dosage forms at 2 hours of medication on the 7th day of treatment

组别	例数	INH[例(%)]			RFP[例(%)]
组别	例数	<3 mg/L	3~6 mg/L	>6 mg/L	<8 mg/L	8~24 mg/L	>24 mg/L
口服组	59	38(64.4)	15(25.4)	6(10.2)	17(28.8)	19(32.2)	23(39.0)
注射组	64	41(64.1)	17(26.6)	6(9.3)	5(7.8)	3(4.7)	56(87.5)
χ²值		0.002	0.021	0.022	9.219	15.825	31.452
P值		0.968	0.886	0.882	0.002	<0.001	<0.001

表4 两组治疗第7天用药2 h后INH、RFP达到目标浓度占比的比较

Tab.4 INH and RFP reaching target concentration after 2 hours of medication on the 7th day of treatment

组别	例数	用药2 h后达目标浓度[例(%)]
组别	例数	INH	RFP
口服组	59	21(35.6)	42(71.2)
注射组	64	23(35.9)	59(92.2)
χ²值		0.002	9.219
P值		0.968	0.002

图1 血药浓度-年龄散点图

Fig.1 Blood concentrations-age scatter plot

表5 多元线性回归分析结果

Tab.5 Multiple linear regression analysis results

自变量	偏回归系数	标准误	标准化偏回归系数	$t$ 值	P值
年龄	-0.043	0.063	-0.176	-2.788	0.006

表5 多元线性回归分析结果

Tab.5 Multiple linear regression analysis results

自变量	偏回归系数	标准误	标准化偏回归系数	$t$ 值	P值
年龄	-0.043	0.063	-0.176	-2.788	0.006

图2 血药浓度-年龄标准化残差图

Fig.2 Blood concentrations-age standardization plot

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