抗疟药咯萘啶在兔体内的药代动力学

本文报道抗疟药咯萘啶iv,im和ig给药后在兔体内的药代动力学。用NONLIN程序对血药—时间数据进行拟合。一次快速iv 6 mg/kg后的血药—时间过程符合线性三室开模型。药代动力学参数(±SD):t 1/2_β为59±10h;V_c2.418±0.287L/kg;V_d(ss),29±6 L/kg;总清除率Cl_T为0.442±0.131 L/kg·h。Im和ig给药后的动力学过程以线性二室开模型描述。im 6 mg/kg,吸收速率常数K_a为33.5±21.8 h^-1,t 1/2_β为52±8 h,吸收完全。Ig 30或60 mg/kg后的k_a为2.41±1.26 h^-1,t 1/2_β为55±5 h,吸收程度为34.6%。咯萘啶在血中呈不均一分布,im后1～96 h,球/浆浓度比为3～6。

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.