Comparative pharmacokinetic, immunologic and hematologic studies on the anti-HIV-1/2 compounds aconitylated and succinylated HSA

AbstractCharge modification by succinylation or cis-aconitylation of the terminal ϵNH2 functions of the amino acid lysine in human serum albumin, resulted in polyanionic compounds with an anti-HIV-1 activity in the low nanomolar concentration range. After iv injections in rats of the negatively charged albumins (NCAs), a dose dependent elimination pattern was observed indicating a saturable eliminations pathway. The Michaelis-Menten parameters Vmax and Km were 62 ± 8 μg.min−1.kg−1 and 16 ± 4 μg.ml−1 (Clintr 3.9 ± 1.1 ml.min−1.kg-1) and 74 ± 6 μg.min−1.kg−1 and 11 ± 2 μg.ml−1 (Clintr 6.7 ± 1.2 ml.min−1.kg−1) for aconitylated-HSA (Aco-HSA) and succinylated-HSA (Suc-HSA) respectively, using 125I-labelled proteins. The volume of distribution (V) of both compounds was approximately 60 ml.kg−1. Coadministration of poly-inosinic acid and formaldehyde treated albumin showed a marked inhibition of blood clearance indicating that the compounds are mainly cleared from the bloodstream by scavenger receptors on liver ...