Novel hyaluronic acid–methotrexate conjugate suppresses joint inflammation in the rat knee: efficacy and safety evaluation in two rat arthritis models

Table 2 Pharmacokinetics parameters for MTX plasma profiles of antigen-induced arthritis after treatment with oral MTX or DK226

Compound	Dose	T_max (h)	C_max (pg/mL)	AUC_inf (ng · h/mL)	t_1/2 (h)
MTX	1.25 mg/kg, oral^a	0.9 ± .0.3	72,600 ± 10,000	365 ± 37	2.78 ± 0.18
DK226	50 μL/body, intra-articular^b	20.0 ± 8.0	1900 ± 180	68.4 ± 6.1	11.2 ± 0.4

AIA rats were dosed with oral MTX (five times a week, day −7 to day 14) or intra-articular DK226 (weekly, day −7 to day 14) to produce a comparable suppression of knee joint swelling. Serial blood samples were collected from AIA rats on day 14 at 0 h (immediately before treatment) and at 0.25, 0.5, 1, 2, 4, 8, and 24 h after treatment with oral MTX, and at 4, 8, 24, 48, and 72 h after treatment with DK226. Plasma concentrations of MTX were then determined by LC-MS/MS. PK parameters were calculated by a non-compartmental model
MTX methotrexate, T _max time to reach maximum plasma concentration, C _max maximum plasma concentration, AUC _inf area under the plasma concentration-time curve calculated from time zero to infinity, t _1/2 terminal phase elimination half-life
^aThe dose of MTX administered; 375 μg
^bThe dose of MTX injected; 13.6 μg

ISSN: 1478-6362