Abstract:
: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.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Allen DD,Orvig C,Yokel RAdoi
10.1016/0300-483x(94)90177-5subject
Has Abstractpub_date
1994-09-06 00:00:00pages
193-202issue
1-3eissn
0300-483Xissn
1879-3185pii
0300-483X(94)90177-5journal_volume
92pub_type
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