Pharmacokinetics of isoniazid and rifapentine in young pediatric patients with latent tuberculosis infection

作者：Weeraya Phaisal, Watsamon Jantarabenjakul, Noppadol Wacharachaisurapol, Monta Tawan, Thanyawee Puthanakit, Supeecha Wittayalertpanya, Pajaree Chariyavilaskul · 发表于：International Journal of Infectious Diseases · 年份：2022 · DOI：10.1016/j.ijid.2022.07.040 · 被引用次数：10 · 研究领域：Tuberculosis Research and Epidemiology、Pneumonia and Respiratory Infections、Malaria Research and Control

Objectives This study investigated the steady-state pharmacokinetic profiles of 3-month weekly rifapentine plus isoniazid (3HP) in children with latent tuberculosisinfection (LTBI). We also assessed other factors, including tablet integrity, food, and pharmacogenetics. Methods During the 3HP treatment, blood and urine samples were collected in week 4. Isoniazid and rifapentine levels were measured using a high-performance liquid chromatography technique. The genetic variation of arylamine N-acetyltransferase 2 ( NAT2 ) and arylacetamide deacetylase ( AADAC ) were assessed by the MassARRAY®. Safety and clinical outcomes at week 48 were monitored. Results A total of 12 children with LTBI (age 3.8 [range 2.1-4.9 years old]) completed the treatment (isoniazid and rifapentine dose 25.0 [range 21.7-26.8] and 25.7 [range 20.7-32.1] mg/kg, respectively). No serious adverse events or active TB occurred. Tablet integrity was associated with decreased area under the concentration-time curve (91 vs 73 mg.h/l, P = 0.026) and increased apparent oral clearance of isoniazid (0.27 vs 0.32 l/h/kg, P = 0.019) and decreased rifapentine's renal clearance (CL R , 0.005 vs 0.003 l/h, P = 0.014). Food was associated with increased CL R of isoniazid (3.45 vs 8.95 l/h, P = 0.006) but not rifapentine. Variability in NAT2 and AADAC did not affect the pharmacokinetics of both drugs. Conclusion There is high variability in the pharmacokinetic profiles of isoniazid and rifapentine in young children with LT...