Pharmacokinetics of OPB-2045 in Rats: Systemic Exposure following Oral, Subcutaneous, and Intravenous Administration

Abstract

1. The pharmacokinetics of OPB-2045, a new antiseptic antimicrobial agent possessing a biguanide moiety in its molecule, was investigated in Sprague-Dawley rats after a single oral, subcutaneous, and intravenous administrations. A high-performance liquid chromatographic method with detection limit of 8 ng/ml was developed and then used to determine serum concentration of the compound.
2. Following single oral doses at 10, 100, and 1, 000 mg/kg, serum OPB-2045 could be detected only at 1, 000 mg/kg with the concentration below 15 ng/ml.
3. The time-courses of serum OPB-2045 were almost flat in rats after subcutaneous administrations of the compound at 1, 3, 10, and 30 mg/kg, and no dose-dependent increase of serum concentration was observed.
4. Adequate OPB-2045 serum profiles following intravenous administrations at 1, 3, and 6 mg/kg could be obtained using a two-compartment open model with AIC of -3.0 ?? -58.1. Serum OPB-2045 after intravenous administration exhibited a biphasic decline with half-lives of 0.25 ?? 0.32 hr in the α-phase and 2.16 ?? 4.07 hrs in the β-phase. The volume of distribution in the β-phase was 9.8 ?? 19.8 l/kg, suggesting considerable diffusion of the compound. Total serum clearance of OPB-2045 was 2.0 ?? 3.9 l/hr/kg.
5. The bioavailability of OPB-2045 after oral administration thus appeared to be lower than that subsequent to subcutaneous administration.