López-Ramos Maria Goretti, Vinent Joan, Aarnoutse Rob, Colbers Angela, Velasco-Arnaiz Eneritz, Martorell Loreto, Falcón-Neyra Lola, Neth Olaf, Prieto Luis, Guillén Sara, Baquero-Artigao Fernando, Méndez-Echevarría Ana, Gómez-Pastrana David, Jiménez Ana Belén, Lahoz Rebeca, Ramos-Amador José Tomás, Soriano-Arandes Antoni, Santiago Begoña, Farré Rosa, Fortuny Clàudia, Soy Dolors, Noguera-Julian Antoni
Pharmacy Department, Hospital Sant Joan de Déu, 08950 Barcelona, Spain.
Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, 6525 HB Nijmegen, The Netherlands.
Antibiotics (Basel). 2023 Jan 30;12(2):272. doi: 10.3390/antibiotics12020272.
In 2010, the WHO recommended an increase in the daily doses of first-line anti-tuberculosis medicines in children. We aim to characterize the pharmacokinetics of the once-daily isoniazid (INH) dose at 10 mg/kg of body weight in infants <6 months of age. We performed a multicenter pharmacokinetic study in Spain. The N-acetyltransferase 2 gene was analyzed to determine the acetylation status. Samples were analyzed using a validated UPLC-UV assay. A non-compartmental pharmacokinetic analysis was performed. Twenty-three pharmacokinetic profiles were performed in 20 infants (8 females) at a median (IQR) age of 19.0 (12.6-23.3) weeks. The acetylator statuses were homozygous fast ( = 1), heterozygous intermediate ( = 12), and homozygous slow ( = 7). INH median (IQR) C and AUC values were 4.8 (3.7-6.7) mg/L and 23.5 (13.4-36.7) hmg/L and the adult targets (>3 mg/L and 11.6-26.3 hmg/L) were not reached in three and five cases, respectively. The age at assessment or acetylator status had no impact on C values, but a larger INH AUC ( = 0.025) and trends towards a longer half-life ( = 0.055) and slower clearance ( = 0.070) were observed in homozygous slow acetylators. Treatment was well tolerated; mildly elevated alanine aminotransferase levels were observed in three cases. In our series of young infants receiving isoniazid, no major safety concerns were raised, and the target adult levels were reached in most patients.
2010年，世界卫生组织建议增加儿童一线抗结核药物的每日剂量。我们旨在描述6个月以下婴儿每日一次服用10mg/kg体重异烟肼（INH）剂量的药代动力学特征。我们在西班牙进行了一项多中心药代动力学研究。分析了N-乙酰转移酶2基因以确定乙酰化状态。使用经过验证的超高效液相色谱-紫外检测法对样本进行分析。进行了非房室药代动力学分析。对20名婴儿（8名女性）进行了23次药代动力学分析，中位（IQR）年龄为19.0（12.6 - 23.3）周。乙酰化状态为纯合快速型（ = 1）、杂合中间型（ = 12）和纯合缓慢型（ = 7）。INH的中位（IQR）C和AUC值分别为4.8（3.7 - 6.7）mg/L和23.5（13.4 - 36.7）hmg/L，分别有3例和5例未达到成人目标值（>3 mg/L和11.6 - 26.3 hmg/L）。评估年龄或乙酰化状态对C值没有影响，但在纯合缓慢乙酰化者中观察到较大的INH AUC（ = 0.025）以及半衰期延长的趋势（ = 0.055）和清除率减慢的趋势（ = 0.070）。治疗耐受性良好；3例观察到丙氨酸氨基转移酶水平轻度升高。在我们这组接受异烟肼治疗的幼儿中，未引发重大安全问题，大多数患者达到了成人目标水平。
