Tu150 - Characterization of Ibudilast Pharmacokinetics in the Rat After Intravenously Administration

Abstract Text:

Background: Ibudilast is a non-specific Phosphodiesterases (PDEs) inhibitor used for inhibiting PDE 3, 4, 10, and 11, which are involved in various cellular and biochemical processes. Previous studies demonstrated ibudilast carries many anti-inflammatory properties and might be a great therapeutic potential for various inflammatory diseases, including amyotrophic lateral sclerosis (ALS). However, there is a lack of information on the pharmacokinetics (PK) of the drug after intravenous (IV) administration, and an IV formulation is needed to determine if its immune inhibition improves organ failure outcomes for polytrauma injuries. Here, we sought to characterize the PK of ibudilast after IV administration in a healthy rat model.

Method: Under general anesthesia, with prophylactic analgesics, 0.5 mg/kg ibudilast was delivered to a group of rats (n=4) via a single IV bolus. Plasma samples were collected at 0, 5, 10, 15, 30, 60, 120, 240, 480, 720, 1440 and 1920 minutes (mins) after drug infusion and quantified using mass spectrometry. Plasma PK parameters were calculated using the non-compartmental analysis (NCA) with PKanalix software.

Results: The Cmax and Tmax of were 8.13±4.59 mM and 0.083 hour, respectively. The AUC0-t and AUC0-∞ were calculated as 5.20±2.86 mM*h and 5.52±3.08 mM*h. The overall clearance was 0.00067±0.00034 L⋅h⁻¹⋅kg⁻¹ with plasma half-life of 1.26±0.57 h (Mean±SE). The Vd was measured as 0.00088±0.00034 L⋅kg-1.

Conclusion: Ibudilast seems to be quickly absorbed in blood after IV injection with a relatively short half-life. The PK data from this study will be used to develop an optimal dose of ibudilast for efficacy studies.