Moore K H, Shaw S, Laurent A L, Lloyd P, Duncan B, Morris D M, O'Mara M J, Pakes G E
Glaxo Wellcome Inc., Research Triangle Park, North Carolina, USA.
J Clin Pharmacol. 1999 Jun;39(6):593-605. doi: 10.1177/00912709922008209.
A single-center, open-label, three-way crossover study was conducted in 24 healthy subjects to assess (1) the bioequivalence of a combined lamivudine 150 mg/zidovudine 300 mg tablet relative to the separate brand-name components administered concurrently and (2) the effect of food on the bioavailability of the drugs from the combination tablet. The subjects were randomly assigned to receive each of the following three treatments, separated by a 5- to 7-day washout period: one lamivudine/zidovudine combination tablet after an overnight fast, one lamivudine 150 mg tablet and one zidovudine 300 mg tablet simultaneously after an overnight fast, or one lamivudine/zidovudine combination tablet 5 minutes after completing a standardized high-fat breakfast (67 g fat, 58 g carbohydrate, and 33 g protein). Serial blood samples were collected up to 24 hours postdose for the determination of lamivudine and zidovudine plasma concentrations. Standard pharmacokinetic parameters were estimated. Treatments were considered bioequivalent if 90% confidence intervals for the ratio of least squares (LS) means for the lamivudine and zidovudine area under the plasma concentration-time curve (AUC infinity) and maximum observed plasma concentration (Cmax) fell entirely within 0.80 to 1.25 for log-transformed parameters. The combined lamivudine/zidovudine tablet was bioequivalent in the extent (AUC infinity) and rate of absorption (Cmax and time of Cmax [tmax]) to the individual brand-name drug components administered concurrently under fasted conditions. Geometric LS mean ratios and 90% confidence intervals for AUC infinity and Cmax were 0.97 (0.92, 1.03) and 0.94 (0.84, 1.06), respectively, for lamivudine and 0.99 (0.91, 1.07) and 0.97 (0.82, 1.15), respectively, for zidovudine. The extent of absorption of lamivudine and zidovudine from the combination tablet was not altered by administration with meals, indicating that this formulation may be administered with or without food. However, food slowed the rate of absorption, delayed the tmax, and reduced the Cmax of lamivudine and zidovudine. These changes were not considered clinically important. All formulations were well tolerated under fasted and fed conditions.
在24名健康受试者中进行了一项单中心、开放标签、三交叉研究，以评估：（1）拉米夫定150毫克/齐多夫定300毫克复方片剂相对于同时服用的各自品牌名成分的生物等效性；（2）食物对复方片剂中药物生物利用度的影响。受试者被随机分配接受以下三种治疗，每种治疗间隔5至7天的洗脱期：禁食过夜后服用一片拉米夫定/齐多夫定复方片剂；禁食过夜后同时服用一片150毫克拉米夫定片和一片300毫克齐多夫定片；或在完成标准化高脂早餐（67克脂肪、58克碳水化合物和33克蛋白质）后5分钟服用一片拉米夫定/齐多夫定复方片剂。给药后长达24小时采集系列血样，以测定拉米夫定和齐多夫定的血浆浓度。估算标准药代动力学参数。如果拉米夫定和齐多夫定血浆浓度-时间曲线下面积（AUC无穷大）和最大观察血浆浓度（Cmax）的最小二乘（LS）均值比值的90%置信区间对于对数转换参数完全落在0.80至1.25范围内，则认为各治疗具有生物等效性。拉米夫定/齐多夫定复方片剂在吸收程度（AUC无穷大）和吸收速率（Cmax以及Cmax出现时间[tmax]）方面与禁食条件下同时服用的各自品牌名药物成分具有生物等效性。拉米夫定的AUC无穷大的几何LS均值比值和90%置信区间分别为0.97（0.92，1.03）和Cmax为0.94（0.84，1.06），齐多夫定的分别为0.99（0.91，1.07）和Cmax为0.97（0.82，1.15）。复方片剂中拉米夫定和齐多夫定的吸收程度不受进餐的影响，这表明该制剂可以与食物同服或空腹服用。然而，食物减慢了吸收速率，延迟了tmax，并降低了拉米夫定和齐多夫定的Cmax。这些变化不被认为具有临床重要性。所有制剂在禁食和进食条件下耐受性良好。
