Prince R A, Johnson J A, Weinberger M M
College of Pharmacy, University of Iowa, Iowa City 52242.
Pharmacotherapy. 1989;9(4):240-4. doi: 10.1002/j.1875-9114.1989.tb04132.x.
To assess fever-induced changes in theophylline pharmacokinetics in the rabbit model, six healthy, male, New Zealand white rabbits were studied using a randomized, matched-pair design. In treatment 1, 15 mg/kg of theophylline was infused into the left marginal ear vein, and several blood samples were collected from the opposite ear for 10 hours. Treatment 2 was conducted in an identical manner, except 20 to 40 micrograms/kg of Escherichia coli endotoxin was injected into the left marginal ear vein to induce fever. The majority of the rabbits had slight decreases in the slowest disposition rate constant and increases in the volume of distribution at steady state; however, total body clearance was only minimally (5%) changed. No statistically significant differences were noted between these values (Hotelling T2 = 0.32). Given the sample and methods, fever apparently does not affect theophylline pharmacokinetics.
为评估在兔模型中发热引起的茶碱药代动力学变化，采用随机配对设计对6只健康雄性新西兰白兔进行了研究。在治疗1中，将15mg/kg的茶碱注入左耳缘静脉，并从对侧耳采集几份血样，持续10小时。治疗2以相同方式进行，只是将20至40微克/千克的大肠杆菌内毒素注入左耳缘静脉以诱导发热。大多数兔子的最慢处置速率常数略有下降，稳态分布容积增加；然而，总体清除率仅发生了极小的变化（5%）。这些值之间未观察到统计学上的显著差异（霍特林T2 = 0.32）。鉴于样本和方法，发热显然不影响茶碱的药代动力学。
