Pharmacokinetics of cantide, an antisense oligonucleotide, and its metabolites in rhesus monkeys

To study the pharmacokinetics of cantide, an antisense oligonucleotide, and its metabolites after iv gtt administration in rhesus monkeys, a dual solid phase extraction pretreatment method coupling with non-gel sieving capillary electrophoresis analysis method was used for determination of cantide and its metabolites in plasma and their pharmacokinetic parameters were calculated.  The pharmacokinetic behavior of cantide and its metabolites (M1 and M2) after iv gtt administration (8, 16 and 24 mg·kg⁻¹) in rhesus monkeys were investigated.  After iv gtt administration of cantide to rhesus monkeys, cantide in plasma was eliminated rapidly and the terminal elimination half-life (t_1/2) was 57.91−77.97 min, the correlation coefficients (r) to the dose of C_max, AUC_0−inf  and AUC_0−t of the prototype was 0.991 8, 0.956 8 and 0.977 3, respectively.  The metabolites of cantide reached the C_max following cantide immediately and the C_max of metabolites were lower than that of the prototype.  The CL_s of cantide and its metabolites (M1 and M2) were 1.60−2.19, 5.92−8.58 and 6.07−8.78 mL·min⁻¹·kg⁻¹, respectively.  So, it is concluded that the C_max of cantide and its metabolites increased with the dose, which is the same as their AUC_0−inf and AUC_0−t.  The CL_s of metabolites were higher than that of the prototype.  The MRT and t_1/2 of metabolites in the high dose group increased obviously.