Galtier M, Bressolle F, de la Coussaye J E, Gomeni R, Joubert P, Gény F, Dubois A, Raffanel C, Saissi G, Eledjam J J
Laboratoire de Pharmacocinétique, Hôpital Carémeau, CHU Nîmes, France.
Clin Pharmacokinet. 1993 Nov;25(5):415-23. doi: 10.2165/00003088-199325050-00007.
Multiple-dose pharmacokinetics of pefloxacin were evaluated in 25 patients with hepatocellular insufficiency. The severity of liver disease was graded A, B or C according to the Child-Pugh classification. Pharmacokinetic parameters evaluated in patients on day 1 of treatment were compared with those computed in 11 healthy volunteers (the control group) after a single dose. Blood samples were taken at frequent intervals after drug administration and assayed by high performance liquid chromatography. The mean age of patients with liver impairment was slightly greater (59.5 years, range 33 to 81 years) than that of the control group (46.7 years, range 42 to 51 years). In the patients with liver disease, the mean (+/- SD) half-life of elimination, although highly variable, was significantly longer (46.3 +/- 42.5 hours) than in the control group (11.3 +/- 3.5 hours, p < 0.001). The total clearance was significantly decreased (1.76 +/- 1.31 L/h vs 6.03 +/- 2.99 L/h in the control group). In groups B and C of the Child-Pugh classification, total body clearance was about 30% of normal values. Elimination half-life increased by 200% in group B and 373% in group C compared with values in healthy volunteers. Intergroup differences (group B vs group C of the Child-Pugh classification) were not statistically significant. The minimum concentrations inhibiting 90% of Gram-negative strains (MIC90) were exceeded by plasma pefloxacin concentrations throughout treatment. For most patients, trough plasma concentrations were above 2 mg/L and peak plasma concentrations averaged 8.5 mg/L. Large inter- and intraindividual variations in the elimination half-life, total clearance and volume of distribution were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
对25例肝细胞功能不全患者的培氟沙星多剂量药代动力学进行了评估。根据Child-Pugh分类法，将肝病严重程度分为A、B或C级。将治疗第1天患者的药代动力学参数与11名健康志愿者（对照组）单次给药后的参数进行比较。给药后频繁采集血样，采用高效液相色谱法进行测定。肝功能损害患者的平均年龄（59.5岁，范围33至81岁）略高于对照组（46.7岁，范围42至51岁）。在肝病患者中，消除半衰期的平均值（±标准差）虽然变化很大，但明显长于对照组（46.3±42.5小时对11.3±3.5小时，p<0.001）。总清除率显著降低（1.76±1.31L/h对对照组的6.03±2.99L/h）。在Child-Pugh分类的B组和C组中，全身清除率约为正常值的30%。与健康志愿者相比，B组消除半衰期增加200%，C组增加373%。组间差异（Child-Pugh分类的B组与C组）无统计学意义。整个治疗过程中，血浆培氟沙星浓度均超过抑制90%革兰阴性菌株的最低浓度（MIC90）。对于大多数患者，血浆谷浓度高于2mg/L，血浆峰浓度平均为8.5mg/L。观察到消除半衰期、总清除率和分布容积存在较大的个体间和个体内差异。（摘要截短于250字）
