Objective: To study the relationship between the weight change trend of initial treatment patients with pulmonary tuberculosis and the dose change trend of isoniazid, and therefore to analyze the appropriate dose of isoniazid. Methods: Data of initial treatment inpatients with pulmonary tuberculosis from May 1955 to December 2012 were retrospectively analyzed. Elderly patients with pulmonary tuberculosis, patients with drug-resistant tuberculosis, extrapulmonary tuberculosis and those with complications were excluded from the study. The time period was separated as 20th century 1950s to 1960s, 1970s, 1980s, 1990s, 21th century 2000s and 2010s. Samples were selected in each year and month between 1950s to 1960s and 1970s. After 1980s, samples of 1 year were taken from each 5 years. The sex, age and weight for every patient were collected, as well as the dose of isoniazid of every inpatient on a day in therapeutic regimen. Meanwhile, the weight change trend of the patients in different ages and the dose change trend of isoniazid were compared. The total number of cases was 1 398, with 924 males and 474 females, averaging (36.7±14.4) years old. Results: The weight of the patients increased when it was compared between that in 1950s to 1960s, 1970s or 1980s and that in 2000s, with a increasing weight of 3 kg, 3.5 kg and 3 kg respectively. The difference showed statistical significance (P<0.003). The difference was also significant when the weight in 70s was compared with that in 2010s (P=0.002). The therapeutic dose of isoniazid remained invariable regardless of the weight change. At 1990s, 2000s and 2010s, the dose of isoniazid per kilogram of body weight would reduce to 0.005 4 g, 0.005 2 g and 0.0054 g relative to patients' weight increase, and the difference was statistically significant (P<0.001). Conclusions: The weight of pulmonary tuberculosis inpatients increased in recent 60 years. The weight has a close relation with the dose of isoniazid. A fixed dose of isoniazid (0.3 g/d) regardless of the weight change could result in low blood drug concentration . To avoid tolerance of isoniazid and increase the cure rates of pulmonary tuberculosis, the dosage of isoniazid should be increased based on the weight increase of patients.
目的： 分析初治肺结核患者体重变化与口服异烟肼剂量的关系，探讨异烟肼使用剂量的合理性。 方法： 采取回顾性调查分析法，收集1955年5月至2012年12月北京胸科医院住院的初治肺结核患者，排除老年性肺结核、耐药肺结核、肺外结核病和各种合并症及并发症患者。选取时间段分为20世纪50—60年代、70年代、80年代、90年代及21世纪2000年代和2010年代；50—60年代和70年代每年每月抽取部分病例，80年代以后每隔5年抽取1年的部分病例，分别统计各时间段纳入患者的性别、年龄、体重和治疗方案中每天应用异烟肼的剂量，比较不同年代住院肺结核患者体重变化趋势与所服异烟肼剂量的变化。共纳入病例1 398例，其中男924例，女474例，年龄18～65岁，平均(36.7±14.4)岁。本研究中不符合正态分布的数据采用秩和检验，检验水准P<0.05。两两比较单样本采用Kolmogorov－Smirnov非参数检验，检验水准α＝0.003。 结果： 2000年代与50—60年代、70年代和80年代比较，患者体重分别增加了3、3.5和3 kg，差异有统计学意义(均P<0.003)；21世纪2010年代与20世纪70年代比较，患者体重平均增加了1.5 kg，差异也有统计学意义(P＝0.002)，而异烟肼治疗的剂量无论体重大小始终未变。90年代、2000年代及2010年代后每公斤体重异烟肼的剂量随着患者体重的增加而逐渐减少了0.005 4、0.005 2及0.005 4 g，且差异有统计学意义(均P<0.001)。 结论： 近60年来，住院肺结核患者的体重呈现逐渐上升趋势，其中体重与异烟肼药物剂量密切相关，无论体重大小常规使用异烟肼0.3 g/d的治疗剂量可能存在血药浓度较低的现象。为防止异烟肼耐药，提高肺结核的治愈率，应根据患者体重的变化适当合理提高异烟肼的治疗剂量。.
Keywords: Body weight; Isoniazid; Tuberculosis, pulmonary.