Reihanikermani H, Ansari M, Soltani A, Meymandi M S
Department of Neurosurgery, Bahonar Hospital and Neuroscience Research Center, Kerman Medical Sciences University, Kerman, Iran.
Indian J Pharm Sci. 2008 Nov;70(6):782-5. doi: 10.4103/0250-474X.49122.
Previous studies have demonstrated that pharmacokinetic behavior of several drugs such as paracetamol, theophylline, and aminoglycosides are significantly altered in spinal cord injured patients. No pharmacokinetic study of amitriptyline has been performed in patients and experimental models of spinal cord injury. Pharmacokinetic parameters of amitriptyline in orally treated rabbits subjected to laminectomy and spinal cord injury compared with those underwent laminectomy alone. Among twenty four male rabbits were included in this study, nine of them subjected to spinal cord injury at the 8(th) thoracic level by knife severance method and six rabbits underwent laminectomy alone (sham group) and nine rabbits treated as control. All received a single oral dose of amitriptyline (20 mg/kg) 24 h after injury. Blood sampling were done at predetermined times to 36 h after drug administration. Amitriptyline concentration in serum samples was determined by high-performance liquid chromatography. Pharmacokinetic parameters including maximum concentration (C(max)), time to reach maximum concentration (T(max)), half life, and the area under the curve to last detectable concentration time point (AUC(0-t)) were directly determined from the concentration-time curve. Maximum concentration was observed at 6.5 h after administration in sham group with a concentration of 439.6 ng/ml, whereas in SCI group T(max) was at 2.7 h with a concentration of 2763.9 ng/ml. In control group it was 3.3 h and 396 ng/ml, respectively. In SCI group, AUC was 9465.6 ng.h/ml and half life was 6 h and for control group it was 2817.4 ng.h/ml and 6.4 h, respectively. Statistical analysis of data showed that SCI didn't induce significant changes in amitriptyline pharmacokinetic parameters.
先前的研究表明，脊髓损伤患者体内几种药物（如对乙酰氨基酚、茶碱和氨基糖苷类药物）的药代动力学行为会发生显著改变。尚未在脊髓损伤患者和实验模型中进行过阿米替林的药代动力学研究。将接受椎板切除术和脊髓损伤的口服治疗兔体内阿米替林的药代动力学参数与仅接受椎板切除术的兔进行比较。本研究纳入了24只雄性兔，其中9只通过刀切断法在第8胸椎水平遭受脊髓损伤，6只兔仅接受椎板切除术（假手术组），9只兔作为对照组。所有兔在损伤后24小时接受单次口服剂量的阿米替林（20mg/kg）。在给药后预定时间至36小时进行采血。通过高效液相色谱法测定血清样本中阿米替林的浓度。药代动力学参数包括最大浓度（C(max)）、达到最大浓度的时间（T(max)）、半衰期以及至最后可检测浓度时间点的曲线下面积（AUC(0-t)），直接从浓度-时间曲线中确定。假手术组在给药后6.5小时观察到最大浓度，为439.6ng/ml，而在脊髓损伤组中T(max)为2.7小时，浓度为2763.9ng/ml。对照组分别为3.3小时和396ng/ml。在脊髓损伤组中，AUC为9465.6ng.h/ml，半衰期为6小时，对照组分别为2817.4ng.h/ml和6.4小时。数据的统计分析表明，脊髓损伤并未引起阿米替林药代动力学参数的显著变化。
