PHARMACOKINETICS OF PYRONARIDINE, AN ANTIMALARIAL IN RABBITS

The pharmacokinetics of pyronaridine, an antimalarial, was studied in rabbits after a single intravenous, intramuscular or intragastric dose. Whole blood concentrations of the drug were measured at various time intervals up to 8 days after administration using a sensitive and specific spectrofluorometric method established preViously. Models were fitted to the blood concentration/time data by NONLIN program. The blood concentration/time data from single intravenous bolus injection of 6 mg/kg were adequately described by a linear three-compartment open model. The pharamacokinetic parameters (±SD) are: t_1/2β, 59±10 h; v_c, 2.418±0.287 L/kg; v_d(ss), 29±6 L/kg; Cl_T, 0.442±0.131 L/kg·h.The pharmacokinetic profiles after intramuscular(6 mg/kg) or intragastric administration (30 and 60 mg/kg) were described by a linear two-compartment open model. When the drug was given intramuscularly, it was absorbed completely, and rapidly as indicated by a k_a 33.54±21.81 h^-1 and T_max 0.75±0.44 h. While the drug was given intragastricaly, it was only 34.6% bioavailable, with a k_a 2.40±1.26 h^-1, and T_max 1.5±0.3 h. The t_1/2β after intramuscular and intragastric administration were found to be 52±8 and 55±5 h respectively.Pyronaridine was not homogeneously distributed in the blood, the blood cell/plasma concentration ratios being 3～6 during 1～96 h after intramuscular dosing.