Pedraz J L, Calvo M B, Gascon A R, Hernandez R, Muriel C, Torres L M, Dominguez-Gil A
Department of Pharmacy, Faculty of Pharmacy, University of Salamanca, Spain.
Br J Anaesth. 1991 Sep;67(3):310-6. doi: 10.1093/bja/67.3.310.
We have studied the pharmacokinetics and distribution of ketamine and its biotransformation products in dogs after extradural administration of ketamine at L4-5. The mean apparent uptake rate constants of ketamine for plasma and CSF were 4.17 (SD 1.84) and 5.15 (2.50) h-1, respectively. The concentrations of ketamine in CSF were greater than those found in plasma. The elimination half-life values of the parent drug for both biological fluids were similar (4.3 (2.96) h and 4.6 (3.31) h for plasma and CSF, respectively). The apparent formation rate constant of norketamine was greater than that of dehydronorketamine. However, the concentrations of the biotransformation products in CSF were smaller than those of the parent drug. These results are similar to the distribution of ketamine and its metabolites in different cerebral structures and tissues. The concentrations decreased in concert with the increase in polarity of the metabolites. A specific distribution for all compounds was observed. Ketamine showed a greater affinity for brainstem, while norketamine and dehydronorketamine were distributed mostly in cerebellum and kidney, respectively.
我们研究了在犬的L4 - 5节段硬膜外给予氯胺酮后，氯胺酮及其生物转化产物的药代动力学、分布情况。氯胺酮在血浆和脑脊液中的平均表观摄取速率常数分别为4.17（标准差1.84）和5.15（2.50）h⁻¹。脑脊液中氯胺酮的浓度高于血浆中的浓度。母体药物在两种生物流体中的消除半衰期值相似（血浆和脑脊液分别为4.3（2.96）h和4.6（3.31）h）。去甲氯胺酮的表观生成速率常数大于脱氢去甲氯胺酮。然而，脑脊液中生物转化产物的浓度低于母体药物。这些结果与氯胺酮及其代谢产物在不同脑结构和组织中的分布情况相似。随着代谢产物极性的增加，浓度相应降低。观察到所有化合物都有特定的分布。氯胺酮对脑干的亲和力更大，而去甲氯胺酮和脱氢去甲氯胺酮分别主要分布在小脑和肾脏。
