Peloquin C A, Namdar R, Dodge A A, Nix D E
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Int J Tuberc Lung Dis. 1999 Aug;3(8):703-10.
To determine the intra- and intersubject variability in and the effects of food or antacids on the pharmacokinetics of isoniazid (INH).
Randomized, four-period cross-over Phase I study in 14 healthy male and female volunteers. Subjects ingested single doses of INH 300 mg under fasting conditions twice, with a high-fat meal, and with aluminum-magnesium antacid. They also received standard doses of rifampin, pyrazinamide, and ethambutol.
Serum was collected for 48 hours, and assayed by high performance liquid chromatography (HPLC). Data were analyzed using noncompartmental methods and a compartmental analysis using nonparametric expectation maximization. Both fasting conditions produced similar results: a mean INH Cmax of 5.53 +/- 2.92 microg/ml, Tmax of 1.02 +/- 1.10 hours, and AUC0-infinity of 20.16 +/- 12.45 microg x hr/ml. These findings are similar to those reported previously. Antacids did not alter these parameters significantly (Cmax of 5.62 +/- 2.53 microg/ml, Tmax of 0.71 +/- 0.56 hours, and AUC0-infinity of 20.27 +/- 11.39 microg x hr/ml). In contrast, the high-fat meal recommended by the Food and Drug Administration reduced INH Cmax by 51% (2.73 +/- 1.70 microg/ml), nearly doubled Tmax (1.93 +/- 1.61 hours), and reduced AUC0-infinity by 12% (17.72 +/- 10.32 microg x hr/ml).
These changes in Cmax, Tmax, and AUC0-infinity can be avoided by giving INH on an empty stomach whenever possible.
确定异烟肼（INH）药代动力学的受试者内和受试者间变异性以及食物或抗酸剂对其的影响。
对14名健康男性和女性志愿者进行的随机、四周期交叉I期研究。受试者在禁食条件下两次服用300毫克单剂量INH，一次与高脂餐同服，一次与铝镁抗酸剂同服。他们还接受了标准剂量的利福平、吡嗪酰胺和乙胺丁醇。
采集血清48小时，并通过高效液相色谱法（HPLC）进行检测。数据采用非房室方法和使用非参数期望最大化的房室分析进行分析。两种禁食条件产生了相似的结果：INH的平均Cmax为5.53±2.92微克/毫升，Tmax为1.02±1.10小时，AUC0至无穷大为20.16±12.45微克·小时/毫升。这些发现与先前报道的相似。抗酸剂未显著改变这些参数（Cmax为5.62±2.53微克/毫升，Tmax为0.71±0.56小时，AUC0至无穷大为20.27±11.39微克·小时/毫升））。相比之下，美国食品药品监督管理局推荐的高脂餐使INH的Cmax降低了51%（2.73±1.70微克/毫升），Tmax几乎翻倍（1.93±1.61小时），AUC0至无穷大降低了12%（17.72±10.32微克·小时/毫升）。
只要有可能，空腹服用INH可避免Cmax, Tmax和AUC0至无穷大的这些变化。
