Sarma G R, Kailasam S, Mitchison D A, Nair N G, Radhakrishna S, Tripathy S P
Tubercle. 1975 Dec;56(4):314-23. doi: 10.1016/0041-3879(75)90087-2.
The suitability of a slow-release matrix preparation of isoniazid for use in once-weekly chemotherapy has been investigated in South Indian patients. Serial plasma isoniazid concentrations were determined up to 6 hours following doses of 15, 30, 45 and 60 mg/kg body-weight in rapid inactivators and up to 10 hours following doses of 15, 30 and 45 mg/kg in slow inactivators. The isoniazid levels were sustained, and the peak concentrations (per unit dose) were considerably lower than with ordinary isoniazid. It was estimated that a matrix isoniazid dose of 35 mg/kg in slow inactivators and 50 mg/kg in rapid inactivators would produce a peak similar to that attained with a non-toxic dose or ordinary isoniazid 15 mg/kg in slow inactivators. A second investigation showed that matrix isoniazid 40 mg/kg in rapid inactivators produced a coverage (with 0.2 mug/ml) and exposure similar to those attained in slow inactivators with a highly effective dose of ordinary isoniazid 15 mg/kg, while 30 mg/kg gave substantially lower values. In both investigations, disproportionately large increases in plasma isoniazid concentrations were observed in rapid inactivators with an increase in the matrix isoniazid dose. In slow inactivators, both doses of matrix isoniazid, 30 and 40 mg/gk, resulted in coverage and exposure that were substantially higher than those obtained with ordinary isoniazid 15 mg/kg.
在南印度患者中研究了异烟肼缓释基质制剂用于每周一次化疗的适用性。对快速灭活者给予15、30、45和60mg/kg体重剂量后，连续测定6小时的血浆异烟肼浓度；对缓慢灭活者给予15、30和45mg/kg剂量后，连续测定10小时的血浆异烟肼浓度。异烟肼水平保持稳定，且（每单位剂量的）峰值浓度明显低于普通异烟肼。据估计，缓慢灭活者服用35mg/kg的基质异烟肼剂量和快速灭活者服用50mg/kg的基质异烟肼剂量所产生的峰值，与缓慢灭活者服用15mg/kg无毒剂量或普通异烟肼所达到的峰值相似。第二项研究表明，快速灭活者服用40mg/kg的基质异烟肼所产生的覆盖范围（0.2μg/ml）和暴露量，与缓慢灭活者服用15mg/kg高效剂量普通异烟肼所达到的相似，而30mg/kg则给出的值明显更低。在两项研究中，快速灭活者随着基质异烟肼剂量的增加，血浆异烟肼浓度出现不成比例的大幅增加。在缓慢灭活者中，30和40mg/gk这两种基质异烟肼剂量所产生的覆盖范围和暴露量，均明显高于15mg/kg普通异烟肼所获得的。
