The aim of the present study was to investigate an eventual influence of the hour of administration on lidocaine kinetics in the rat. 280 Wistar AF SPF adult male rats were used for this study and maintained under controlled environmental conditions (LD: 06.00-18.00) during the month of October. A single 50 mg . kg-1 dose of lidocaine was given by intramuscular route, at four different fixed time points of a 24-hour period (i.e.: 10.00, 16.00, 22.00 and 04.00) to 70 rats. At each specified time point blood samples were taken 5, 15, 30 min., 1, 2, 4 and 6 hours after the drug administration. Lidocaine plasma levels (free and bound) were determinated according to a specific gas chromatographic method. 2. Our data showed circadian variations of pharmacokinetic parameters (Formula: see text) 3. Lidocaine free fraction varied with time and the protein binding of lidocaine showed a circadian variation. 4. The observed variations may be related to 1) daily fluctuations of absorption or binding of the drug 2) to diurnal variation of the hepatic drug metabolising enzymes responsible for the inactivation of the drug and/or 3) to diurnal variations in excretion rate of lidocaine. Finally our results agree with those of Lutsch and Morris who found a circadian periodicity in susceptibility to lidocaine in the mouse with maximal convulsant activity at 21.00.
摘要
本研究的目的是调查给药时间对大鼠利多卡因动力学的潜在影响。本研究使用了280只Wistar AF SPF成年雄性大鼠，并于10月份在可控环境条件下（光照周期：06:00 - 18:00）进行饲养。将70只大鼠分为四组，每组分别于24小时周期内的四个不同固定时间点（即：10:00、16:00、22:00和04:00）通过肌肉注射给予单剂量50 mg·kg⁻¹的利多卡因。在每个指定时间点，于给药后5、15、30分钟、1、2、4和6小时采集血样。根据特定的气相色谱法测定利多卡因血浆水平（游离和结合型）。2. 我们的数据显示药代动力学参数存在昼夜变化（公式：见原文）。3. 利多卡因的游离分数随时间变化，其蛋白结合呈现昼夜变化。4. 观察到的这些变化可能与以下因素有关：1）药物吸收或结合的每日波动；2）负责药物失活的肝脏药物代谢酶的昼夜变化；和/或3）利多卡因排泄率的昼夜变化。最后，我们的结果与Lutsch和Morris的结果一致，他们发现小鼠对利多卡因的敏感性存在昼夜周期性，在21:00时惊厥活性最高。
