Peloquin C A, Bulpitt A E, Jaresko G S, Jelliffe R W, James G T, Nix D E
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Pharmacotherapy. 1998 Nov-Dec;18(6):1205-11.
To determine intrasubject and intersubject variability in, and the effects of food and antacids on, the pharmacokinetics of pyrazinamide (PZA).
Randomized, four-period, crossover phase I study.
Fourteen healthy men and women volunteers.
Subjects ingested single doses of PZA 30 mg/kg under fasting conditions twice, without a high-fat meal and with an aluminum-magnesium antacid. They also received standard dosages of isoniazid, rifampin, and ethambutol.
Serum was collected for 48 hours and assayed by gas chromatography with mass selective detector. Data were analyzed by noncompartmental methods and a compartmental analysis using nonparametric expectation maximization. Both fasting conditions produced similar results: mean PZA Cmax 53.4+/-10.4 microg/ml, Tmax 1.43+/-1.06 hours, and AUC(0-infinity) 673+/-79.7 microg x hr/ml. Fasting results are similar to those in previous reports. In the presence of antacids, subjects had a mean Cmax of 55.6+/-9.0 microg/ml, Tmax of 1.43+/-1.23 hours, and AUC(0-infinity) of 628+/-88.4 microg x hr/ml. In the presence of the high-fat meal, mean Cmax was 45.6+/-9.44 pg/ml, Tmax 3.09+/-1.74 hours, and AUC(0-infinity) 687+/-116 microg x hr/ml.
These small changes in Cmax, Tmax, and AUC(0-infinity) can be avoided by giving PZA on an empty stomach whenever possible.
确定吡嗪酰胺（PZA）药代动力学的个体内和个体间变异性，以及食物和抗酸剂对其的影响。
随机、四周期、交叉I期研究。
14名健康男性和女性志愿者。
受试者在禁食条件下两次服用单剂量30mg/kg的PZA，一次无高脂餐，一次同时服用铝镁抗酸剂。他们还接受了标准剂量的异烟肼、利福平和乙胺丁醇。
采集48小时的血清，采用带质量选择检测器的气相色谱法进行检测。数据通过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。两种禁食条件下结果相似：PZA平均Cmax为53.4±10.4μg/ml，Tmax为1.43±1.06小时，AUC(0-∞)为673±79.7μg·hr/ml。禁食结果与既往报道相似。在服用抗酸剂的情况下，受试者的平均Cmax为55.6±9.0μg/ml，Tmax为1.43±1.23小时，AUC(0-∞)为628±88.4μg·hr/ml。在高脂餐情况下，平均Cmax为45.6±9.44μg/ml，Tmax为3.09±1.74小时，AUC(0-∞)为687±116μg·hr/ml。
只要有可能，空腹服用PZA可避免Cmax、Tmax和AUC(0-∞)出现这些微小变化。
