Hu O Y, Tang H S, Chang C L
School of Pharmacy, National Defence Medical Centre, Taipei, Republic of China.
Biopharm Drug Dispos. 1994 Oct;15(7):563-76. doi: 10.1002/bdd.2510150704.
Cefoperazone is a semisynthetic cephalosporin antibiotic containing a piperazine side chain, which results in antipseudomonal activity. Unlike the other cephalosporins, it is mainly cleared by the liver (60-80%) and it may be more sensitive to changes in the liver function and/or plasma protein binding than other cephalosporins, which are not primarily cleared by the liver. In order to study the influence of chronic lobular hepatitis on the pharmacokinetics of cefoperazone, a dose of 1 g of cefoperazone was administered to 11 normal, healthy volunteers and 16 subjects with chronic lobular hepatitis. In each volunteer or patient, a novel galactose single-point (GSP) method, the galactose elimination capacity (GEC) test, and the modified galactose elimination capacity (MGEC) test were also performed as a measure of residual liver function. Cefoperazone was administered intravenously over a period of 3-5 min. Blood and urine samples were collected at appropriate intervals after drug administration and stored at -30 degrees C until high-pressure liquid chromatographic (HPLC) analysis. The cefoperazone hepatic clearance, mean residence time, and renal clearance in hepatitis patients were significantly different from those of normal healthy volunteers, whereas the plasma protein binding was unaltered between the two groups. Urinary excretion of cefoperazone showed a highly significant increase in patients, 23.95 +/- 5.06% and 37.54 +/- 13.61% for normal men and hepatitis patients respectively. Hepatic clearance and fraction excreted in urine significantly correlated with values of GSP and MGEC respectively (p < 0.05). These results suggest (i) cefoperazone kinetics was significantly altered in patients with chronic lobular hepatitis; (ii) GSP, a novel simple, clinically useful quantitative liver function test, can predict the cefoperazone hepatic clearance in patients with liver dysfunction.
头孢哌酮是一种含有哌嗪侧链的半合成头孢菌素抗生素，具有抗假单胞菌活性。与其他头孢菌素不同，它主要通过肝脏清除（60 - 80%），并且与其他主要不是通过肝脏清除的头孢菌素相比，它可能对肝功能变化和/或血浆蛋白结合更敏感。为了研究慢性小叶性肝炎对头孢哌酮药代动力学的影响，给11名正常健康志愿者和16名慢性小叶性肝炎患者静脉注射1g头孢哌酮。在每位志愿者或患者中，还进行了一种新的半乳糖单点（GSP）方法、半乳糖清除能力（GEC）试验和改良半乳糖清除能力（MGEC）试验，作为残余肝功能的指标。头孢哌酮在3 - 5分钟内静脉给药。给药后在适当时间间隔采集血样和尿样，并在-30℃保存直至高压液相色谱（HPLC）分析。肝炎患者的头孢哌酮肝脏清除率、平均驻留时间和肾脏清除率与正常健康志愿者有显著差异，而两组之间的血浆蛋白结合未改变。头孢哌酮的尿排泄在患者中显著增加，正常男性和肝炎患者分别为23.95±5.06%和37.54±13.61%。肝脏清除率和尿中排泄分数分别与GSP和MGEC值显著相关（p<0.05）。这些结果表明：（i）慢性小叶性肝炎患者的头孢哌酮动力学显著改变；（ii）GSP是一种新的简单、临床有用的定量肝功能试验，可预测肝功能不全患者的头孢哌酮肝脏清除率。
