García-López P, Pérez-Urizar J, Madrazo I, Guízar-Sahagún G, Castañeda-Hernández G
Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, D. F., Mexico.
Biopharm Drug Dispos. 1997 Apr;18(3):203-11. doi: 10.1002/(sici)1099-081x(199704)18:3<203::aid-bdd11>3.0.co;2-f.
The purpose of the present study was to examine the time dependence of oral paracetamol (acetaminophen) bioavailability in an experimental model of spinal cord injury (SCI). Female Sprague-Dawley rats were subjected to spinal cord contusion at the T8-T9 level by the weight drop method producing permanent paraplegia. Oral paracetamol bioavailability after administration of a single 100 mgkg-1 dose was determined 1, 12, and 50 d after SCI. Cmax and AUC were significantly decreased 1 d after SCI compared to sham-injured controls. This reduction, however, was temporary, as there was a recovery of bioavailability parameters which was partial 12 d after SCI, being complete by day 50. The present results confirm the usefulness of animal models for the characterization of the effect of SCI in drug kinetics. Data show that SCI induces significant changes in paracetamol pharmacokinetics. Nonetheless, despite the fact of a permanent loss of functions related to locomotion, pharmacokinetic alterations evolved with time.
本研究的目的是在脊髓损伤（SCI）实验模型中研究口服对乙酰氨基酚（扑热息痛）生物利用度的时间依赖性。通过重物坠落法在T8 - T9水平对雌性Sprague-Dawley大鼠造成脊髓挫伤，导致永久性截瘫。在脊髓损伤后1、12和50天测定单次给予100 mgkg-1剂量后口服对乙酰氨基酚的生物利用度。与假损伤对照组相比，脊髓损伤后1天Cmax和AUC显著降低。然而，这种降低是暂时的，因为生物利用度参数在脊髓损伤后12天部分恢复，到第50天完全恢复。目前的结果证实了动物模型在表征脊髓损伤对药物动力学影响方面的有用性。数据表明，脊髓损伤会引起对乙酰氨基酚药代动力学的显著变化。尽管如此，尽管与运动相关的功能永久性丧失，但药代动力学改变随时间演变。
