Baggot J D
Aust J Exp Biol Med Sci. 1977 Dec;55(6):663-70. doi: 10.1038/icb.1977.66.
Pharmacokinetic parameters which describe distribution and elimination of sulfadimethoxine were determined in cats. Following intravenous administration of a single dose (55 mg/kg), disposition of the drug was described in terms of the biexponential expression: Cp = Ae-alphat + Be-betat. Based on total (free and bound) sulfonamide levels in the plasma, pseudodistribution equilibrium was slowly attained and the half-time of elimination (half-life) was 10.16 h +/- 2.50 (S.D., n = 6). Body clearance, which is the sum of all clearance processes, was 18.8 +/- 4.6 ml kg-1 h-1. Plasma protein binding, measured by equilibrium dialysis at sulfonamide concentration of 50 microgram/ml, was extensive (87.5% +/- 6.3, n =10). Computer-generated curves for an animal representative of the group, based on individual rate constants associated with the two-compartment open model, showed that 12% and 5% of the dose were present in the central and peripheral compartments, respectively, 24 h after administering the drug. A satisfactory dosage regimen might consist of a priming dose (55 mg/kg) and maintenance dosage (27.5 mg/kg at 24 h dosage intervals). Predicted plasma sulfadimethoxine concentrations would oscillate between 125 and 25 microgram/ml during the steady state. Influence of bacterial disease and febrile states on predicted levels remains to be verified experimentally.
在猫身上测定了描述磺胺二甲氧嘧啶分布和消除的药代动力学参数。静脉注射单剂量(55毫克/千克)后,药物的处置情况用双指数表达式描述:Cp = Ae-αt + Be-βt。根据血浆中总(游离和结合)磺胺水平,伪分布平衡达到缓慢,消除半衰期为10.16小时±2.50(标准差,n = 6)。机体清除率是所有清除过程的总和,为18.8±4.6毫升·千克⁻¹·小时⁻¹。在磺胺浓度为50微克/毫升时通过平衡透析测定的血浆蛋白结合率很高(87.5%±6.3,n = 10)。根据与二室开放模型相关的个体速率常数为该组的一只代表性动物生成的计算机曲线显示,给药24小时后,12%和5%的剂量分别存在于中央室和周边室。一个满意的给药方案可能包括一个首剂量(55毫克/千克)和维持剂量(27.5毫克/千克,给药间隔为24小时)。在稳态期间,预测的血浆磺胺二甲氧嘧啶浓度将在125至25微克/毫升之间波动。细菌疾病和发热状态对预测水平的影响仍有待通过实验验证。