Obeng E K, Vallner J J, Cadwallader D E, Tackett R L
Biopharm Drug Dispos. 1987 Mar-Apr;8(2):125-32. doi: 10.1002/bdd.2510080204.
The pharmacokinetics of total and free tiazofurin, an antineoplastic agent, was studied in healthy mongrel dogs following intravenous and oral administration of the drug. The free fraction of tiazofurin was obtained from plasma by an ultrafiltration technique using a micropartition system. Total and free tiazofurin levels were determined by a sensitive high performance liquid chromatographic method. The percentage of tiazofurin bound to plasma proteins remained constant at approximately 15 per cent following administration to healthy mongrel dogs. The mean pharmacokinetic parameters of elimination rate constant (K), effective half-life (t 1/2), mean residence time (MRT) and the time to reach peak plasma level (tmax--after oral administration) were 0.32 +/- 0.04 h-1, 2.24 +/- 0.25 h, 3.23 +/- 0.36 h, and 1.78 +/- 0.50 h, respectively. The apparent volume of distribution at steady state was 0.98 +/- 0.30 1 kg-1 and the plasma clearance was 5.24 +/- 2.39 ml min-1 kg-1. About 90 per cent of tiazofurin was absorbed following oral administration. The pharmacokinetic parameters did not differ significantly between the total and free drug levels, indicating that the pharmacokinetics of total tiazofurin levels reflect those of the free tiazofurin in plasma.
在健康杂种犬静脉注射和口服抗肿瘤药物噻唑呋林后，对其总药物和游离药物的药代动力学进行了研究。噻唑呋林的游离部分通过使用微型分配系统的超滤技术从血浆中获得。总噻唑呋林和游离噻唑呋林水平通过灵敏的高效液相色谱法测定。在给健康杂种犬给药后，与血浆蛋白结合的噻唑呋林百分比保持在约15%的恒定水平。消除速率常数（K）、有效半衰期（t1/2）、平均驻留时间（MRT）以及达到血浆峰浓度的时间（口服给药后的tmax）的平均药代动力学参数分别为0.32±0.04 h-1、2.24±0.25 h、3.23±0.36 h和1.78±0.50 h。稳态时的表观分布容积为0.98±0.30 l kg-1，血浆清除率为5.24±2.39 ml min-1 kg-1。口服给药后约90%的噻唑呋林被吸收。总药物水平和游离药物水平之间的药代动力学参数没有显著差异，这表明总噻唑呋林水平的药代动力学反映了血浆中游离噻唑呋林的药代动力学。
