Treatment1-a | R1 | R2 | Do/a1-b Free Chelator | Do/a1-b Chelator·Al Complex | Dose | AUC1-c |
---|---|---|---|---|---|---|
mg/kg | mmol/liter/hr | |||||
Al-loaded rabbits | ||||||
CP40 (N = 6)1-d | —(CH2)2OH | —CH3 | All in aqueous | All in aqueous | 126.7 | 1.26 |
CP20 (N = 7) | —CH3 | —CH3 | 0.094 | 0.0009 | 106.75 | 0.62 |
CP93 (N = 8) | —CH3 | —CH2CH3 | 0.28 | 0.007 | 152.3 | 0.36 |
CP52 (N = 8) | —(CH2)3OCH2CH3 | —CH3 | 0.68 | 0.2 | 371.3 | 0.14 |
CP94 (N = 8) | —CH2CH3 | —CH2CH3 | 2.1 | 2.1 | 147.7 | 0.24 |
CP24 (N = 3) | —(CH2)3CH3 | —CH3 | 1.5 | 17 | 217.6 | 0.30 |
DFO (N = 9) | <0.0007 | <0.0006 | 98.5 | |||
Saline (N = 8) (the Al lactate-saline group) | ||||||
Non–Al-loaded rabbits | ||||||
Saline (N = 8) (the Na lactate-saline group) |
Doses were selected to yield an AUC equivalent to an iv systemic dose of 450 μmol HP/kg. This dose was obtained by dividing 450 μmol/kg by the systemic bioavailability (17). The DFO dose was 150 μmol/kg. The dose of the HPs is based on the 3:1 HP · Al complex (43), whereas a 1:1 DFO · Al complex is formed.
↵1-a Code numbers, synonyms, and Chemical Abstract Service (CAS) Registry numbers are as follows: CP40, EL1NEt2′ (OH); CP20, L1 HP4A, Hdpp, DMPH, CGP 37 391, deferiprone, CAS Reg. No. 30652-11-0; CP93, EL1; CP52, L1NEtOPr; CP94, EL1NEt; CP24, Hnbp.
↵1-b Do/a, Lipophilicity of the free chelator and its complex with Al, determined as the equilibrium distribution coefficient between n-octanol and an aqueous phase at pH 7.4 (from ref. 51).
↵1-c AUC, Area under the concentrationvs. time curve after iv dosing of 450 μmol HP/kg (from ref. 17).
↵1-d N, Number of rabbits studied.