Gidal B E, Maly M M, Kowalski J W, Rutecki P A, Pitterle M E, Cook D E
School of Pharmacy and Department of Neurology, University of Wisconsin, Madison 53706, USA.
Ann Pharmacother. 1998 Apr;32(4):405-9. doi: 10.1345/aph.17281.
To compare the oral absorption profile of gabapentin following administration of the contents of opened capsules that were mixed with food vehicles of varied macronutrient (protein) composition.
An unblinded, randomized, single-dose, four-way crossover pharmacokinetic study in nine healthy adult men and women volunteers.
Following an overnight fast, a single 600-mg dose of gabapentin (2 x 300-mg Neurontin capsules) was given either as an intact capsule swallowed with 120 mL of tap water (control, phase I), or after capsule contents were opened and mixed with; 4 oz. of applesauce (phase II), 120 mL of orange juice (phase III), or 4 oz. of fat-free chocolate pudding (phase IV). Subjects fasted for 4 hours following drug ingestion. Serial venous blood samples were obtained over 24 hours to determine gabapentin serum concentrations. Pharmacokinetic variables including AUC, maximum serum concentration (Cmax), and time to maximum serum concentration (tmax) were calculated by using standard noncompartmental methods. Subjects served as their own controls, and were randomly crossed over following a minimum 7-day washout period. Statistical analysis was performed by using ANOVA and Student's t-test where appropriate.
No statistically significant differences in any kinetic variable were found between any study arm. A trend was noted for a modest increase in both Cmax and AUC in phase IV (chocolate pudding) compared with control (+18.6% and +13.2%, respectively). In a comparison of protein (phase IV) versus nonprotein phases (phases I-III), gabapentin AUC was 26% greater (47.28+/-14.65 vs. 37.43+/-9.78 microg/mL x h; p = 0.03), and Cmax was 32% higher (4.72+/-1.04 vs. 3.56+/-0.92 microg/mL; p = 0.003).
Opening and mixing the contents of gabapentin capsules does not significantly impair drug absorption. This may be a viable administration option for patients who are unable to swallow intact capsules. Dietary macronutrient composition (i.e., protein) may favorably influence gabapentin oral absorption.
比较加巴喷丁胶囊内容物与不同常量营养素（蛋白质）组成的食物载体混合后口服的吸收情况。
一项针对9名健康成年男性和女性志愿者的非盲、随机、单剂量、四交叉药代动力学研究。
过夜禁食后，给予单剂量600mg加巴喷丁（2粒300mg的Neurontin胶囊），要么整粒胶囊用120mL自来水吞服（对照组，第一阶段），要么打开胶囊内容物并与以下物质混合：4盎司苹果酱（第二阶段）、120mL橙汁（第三阶段）或4盎司无脂巧克力布丁（第四阶段）。服药后受试者禁食4小时。在24小时内采集系列静脉血样以测定加巴喷丁血清浓度。采用标准非房室方法计算药代动力学变量，包括曲线下面积（AUC）、最大血清浓度（Cmax）和达最大血清浓度时间（tmax）。受试者自身作为对照，在至少7天的洗脱期后随机交叉。在适当情况下，采用方差分析和学生t检验进行统计分析。
各研究组之间在任何动力学变量上均未发现统计学显著差异。与对照组相比，第四阶段（巧克力布丁）的Cmax和AUC均有适度增加的趋势（分别增加18.6%和13.2%）。在蛋白质组（第四阶段）与非蛋白质组（第一至三阶段）的比较中，加巴喷丁的AUC高26%（47.28±14.65对37.43±9.78μg/mL·h；p = 0.03），Cmax高32%（4.72±1.04对3.56±0.92μg/mL；p = 0.003）。
打开并混合加巴喷丁胶囊内容物不会显著损害药物吸收。对于无法吞咽整粒胶囊的患者，这可能是一种可行的给药选择。膳食常量营养素组成（即蛋白质）可能对加巴喷丁的口服吸收有有利影响。
