Allen D D, Orvig C, Yokel R A
College of Pharmacy, University of Kentucky Medical Center, Lexington 40536-0082.
Toxicology. 1994 Sep 6;92(1-3):193-202. doi: 10.1016/0300-483x(94)90177-5.
The pharmacokinetics of selected aluminum-hydroxypyridinone (Al-HP complexes were determined in rats to better understand the relationship between their disposition and elimination parameters and the safety of HPs in the chelation therapy of Al intoxication. Five complexes were administered as i.v. bolus doses of Al-HP (0.25 mmol/kg Al-0.75 mmol/kg HP). The Al-HP steady state volumes of distribution ranged from 220 to 871 ml/kg, suggesting that each complex distributed out of the vascular compartment (which should have been approximately 65 ml/kg). Systemic clearances ranged from 189 to 906 ml/h per kg. Elimination half-lives (t1/2) and mean residence times ranged from 0.36 to 0.84 and 0.52 to 1.20 h, respectively. The Al-CP20 complex had a short t1/2 and a midrange volume of distribution. It demonstrated no apparent toxicity, whereas myoclonic seizures were observed after Al-CP22, Al-CP24 and Al-CP94 administration. The most appropriate choice for Al chelation among the HPs tested may be CP20. Characterization of the distribution and elimination of Al-HP complexes improves the understanding of potential toxicity that may be associated with HP therapy of Al intoxication.
为了更好地理解选定的氢氧化吡啶酮铝（Al-HP）配合物的处置和消除参数与HP在铝中毒螯合治疗中的安全性之间的关系，在大鼠中测定了它们的药代动力学。以静脉推注剂量给予五种配合物Al-HP（0.25 mmol/kg铝-0.75 mmol/kg HP）。Al-HP的稳态分布容积范围为220至871 ml/kg，这表明每种配合物都分布在血管腔室之外（血管腔室本应约为65 ml/kg）。全身清除率范围为每千克189至906 ml/h。消除半衰期（t1/2）和平均驻留时间分别为0.36至0.84小时和0.52至1.20小时。Al-CP20配合物的t1/2较短且分布容积处于中等范围。它没有表现出明显的毒性，而在给予Al-CP22、Al-CP24和Al-CP94后观察到肌阵挛性癫痫发作。在所测试的HP中，用于铝螯合的最合适选择可能是CP20。对Al-HP配合物的分布和消除进行表征有助于更好地理解可能与HP治疗铝中毒相关的潜在毒性。
