Detection and plasma pharmacokinetics of an anti-vascular endothelial growth factor oligonucleotide-aptamer (NX1838) in rhesus monkeys

Aptamers are oligonucleotide ligands selected, in vitro, to bind a specifie d target protein. The first aptamer to reach human clinical testing is NX18 38, a polyethylene glycol conjugated aptamer that inhibits vascular endothe lial growth factor. This paper describes the validation of a high-performan ce liquid chromatographic anion-exchange method for the determination of NX 1838 in plasma. Measurements of intact NX1838 had a coefficient of variatio n of less than 8% and an accuracy between 107% and 115%. The assay was util ized to determine NX1838 plasma pharmacokinetics in rhesus monkeys followin g a single 1 mg/kg intravenous or subcutaneous dose. Following intravenous administration, the maximum achieved plasma concentration was 25.5 mu g/ml with a terminal half-life of 9.3 h and clearance rate of 6.2 ml/h, After su bcutaneous administration, the fraction of the dose absorbed into the plasm a compartment was 0.78 with a time to peak concentration (4.9 mu g/ml) of 8 to 12 h. (C) 1999 Elsevier Science B.V. All rights reserved.