The objective of this study was to determine the pharmacokinetics (PK) of oral (OS; 20 mg/kg) and compounded intravenous (IV; 5.5 mg/kg) gabapentin in 6 healthy, adult, Duroc pigs. Subjects were randomized to receive IV and OS gabapentin in a cross-over design, with at least 14 days of wash-out period between the two rounds of drug administrations. Blood samples were obtained before gabapentin administration and at various times up to 24 h, and harvested plasma was stored at −80°C until analysis. Concentration of gabapentin was quantified using a previously validated liquid chromatography/tandem mass spectrometry method, and compartment models were fitted to time-concentration data using non-linear mixed effect (population) analysis. A two-compartment model best fitted the data following IV administration. Typical values for volume of the central compartment and clearance and calculated volume of distribution at steady-state and terminal half-life were 170 ml/kg, 1.2 ml/(kg*min), and 594 ml/kg and 360 min, respectively. For the oral route, absorption half-life, estimated maximal plasma concentration and time to reach maximal plasma concentration were 58 min, 9155 ng/ml, and 194 min, respectively. Estimated oral bioavailability was 47%. Short-lived sedation (approximately 15 min) with sternal or lateral recumbency after IV administration was observed in all subjects without adverse clinical effects. Simulation based on the results of this study suggests that a first oral gabapentin dose of 15 mg/kg and subsequent doses of 8.5 mg/kg every 8 h would achieve and maintain plasma concentrations between 5 and 8 μg/ml in pigs.

中文翻译：

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口服和复方静脉加巴喷丁在杜洛克猪（Sus Scrofa）中的药代动力学

本研究的目的是确定在 6 头健康成年杜洛克猪中口服（OS；20 mg/kg）和复合静脉注射（IV；5.5 mg/kg）加巴喷丁的药代动力学 (PK)。受试者随机接受 IV 和 OS 加巴喷丁交叉设计，两轮给药之间至少有 14 天的洗脱期。在加巴喷丁给药前和最多 24 小时的不同时间采集血样，并将采集的血浆储存在 -80°C 直至分析。使用先前验证的液相色谱/串联质谱法对加巴喷丁的浓度进行量化，并且使用非线性混合效应（群体）分析将隔室模型拟合到时间-浓度数据。两室模型最适合 IV 给药后的数据。在稳态和终末半衰期的中央隔室容积和清除率和计算分布容积的典型值分别为 170 ml/kg、1.2 ml/(kg*min) 和 594 ml/kg 和 360 min。对于口服途径，吸收半衰期、估计的最大血浆浓度和达到最大血浆浓度的时间分别为 58 分钟、9155 ng/ml 和 194 分钟。估计的口服生物利用度为 47%。在所有受试者中观察到 IV 给药后胸骨或侧卧的短暂镇静（约 15 分钟），没有不良临床反应。基于该研究结果的模拟表明，首次口服加巴喷丁剂量为 15 mg/kg，随后每 8 小时口服 8.5 mg/kg，猪的血浆浓度将达到并维持在 5 至 8 μg/ml 之间。