Abstract
Objective To explore the inter-individual deviation of plasma concentrations of three anti-tubercular drugs,and the relationship with age and sex.Methods A total of 557 tuberculosis patients undergoing plasma concentration monitoring of anti-tubercular drugs (TDM) between November 2015 and December 2015 were collected from Xi'an Chest Hospital information managing system.They were divided into isoniazid (INH) group (n=238),rifampicin (RFP) group (n=188) and pyrazinamide (PZA) group (n=131).In INH group,157 were male,81 were female,34 patients were at the age of 15-19 years old,143 patients were at the age of 20-49 years old,and 61 patients were older than 50 years old;in RFP group,the data were 123,65,24,124 nd 40;and in PZA group,the data were 87,44,21,85 and 25.Differences of plasma concentration of the above three drugs and in samples at different ages or with different gender were analyzed by ANOVA and t-test using SPSS 18.0 software.P＜0.05 was considered statistically significant.Results The average concentrations of INH,RFP and PZA were (4.09±2.55) μg/ml,(10.47±3.84) μg/ml and (24.40 ± 10.23) μg/ml,the S2 were 0.34,0.13 and 0.16,respectively,differences were statistically significant (F =13.63,P＜ 0.01).Differences among various ages in INH group were statistically significant (15-19 years old:(5.2(0 ± 3.16) μg/ml,20-49 years old:(3.93 ±2.17)μg/ml,≥50 years old:(3.96 ± 2.27) μg/ml;F=4.11,P=0.018),while the difference between male ((3.96±2.27)μg/ml) and female ((4.34±3.03)μg/ml) was not statistically significant (t=1.09,P=0.277).Of the three analyzed drugs,the concentrations of INH had the largest inter-individual deviation (-x=4.09 μg/ml,S=2.55μg/ml).In RFP group,the mean drug concentration in female ((11.96±4.38) μg/ml) was significantly higher than that in male ((9.68±3.28) μg/ml) (t=3.69,P＜0.01);while there was no statistically significant difference in various ages (15-19 years old:(9.93±3.02)μg/ml,20-49 years old:(10.40±3.75)μg/ml,≥50years old:(11.01±4.51)μg/ml;F=0.66,P=0.518).The variance of RFP concentrations was significantly larger in female (S2 =19.14) than that in male (S2 =10.73) (F=7.37,P=0.007),and was also significantly larger in patients aged ≥50 years (S2 =20.38) than in those who aged other years old (S215-19 years old =9.14,S2200-49 years old =14.07) (F=3.27,P =0.040).The average concentration of PZA was significantly higher in female ((28.97 ±12.12)μg/ml) than in male ((22.08± 8.28) μg/ml) (t=3.83,P＜0.01),but had no statistically significant difference (F=2.26,P=0.109) in samples with different ages (15-19 years old:(28.13±13.70)μg/ml,20-49 years old:(23.15±8.77) μg/ml,≥50 years old:(24.91±9.05)μg/ml).Conclusion There are considerable inter-individual deviations in the blood plasma concentrations of all the three anti-tubercular drugs,therefore,it is essential to implement TDM during clinical therapies when providing personalized treatment plan.Since the inter-individual deviation in concentrations of INH is significantly different,more attention should be paied when INH used.关键词
抗生素类,抗结核/药物监测/药代动力学/个体化医学/药物疗法管理Key words
Antibiotics, antitubercular/Drug monitoring/Pharmacokinetics/Individualized medicine/Medication therapy management
