Spino M, Chai R P, Isles A F, Thiessen J J, Tesoro A, Gold R, MacLeod S M
J Pediatr. 1984 Nov;105(5):829-35. doi: 10.1016/s0022-3476(84)80317-0.
Because of reports of lowered antibiotic serum concentrations in patients with cystic fibrosis (CF), a bioavailability and pharmacokinetic study of cloxacillin was conducted in 12 control and 16 patients with CF after intravenously and orally administered doses of cloxacillin 25 mg/kg. The patients had mild to moderate CF and were in stable condition. Significantly lower serum concentrations in CF were a result of a 78% increase in total body clearance (P less than 0.005) and a 38% increase in the apparent volume of distribution (P less than 0.025). The bioavailability in CF (0.50) was not significantly different than in controls (0.38), but more variability was seen in the group with CF. After the intravenously given dose the fraction of cloxacillin excreted in the urine unchanged was similar in controls (0.644) and patients with CF (0.547). Compared with that in the control subjects, the mean renal clearance in patients with CF was 30% greater (P less than 0.10) and the nonrenal clearance was 144% greater (P less than 0.07). Enhanced nonrenal clearance explains most of the demonstrated difference between serum concentrations in controls and patients with CF after identical weight-adjusted doses. The data suggest enhanced cloxacillin biotransformation in CF.
由于有报道称囊性纤维化（CF）患者的抗生素血清浓度降低，因此在12名对照者和16名CF患者中进行了一项氯唑西林的生物利用度和药代动力学研究，静脉和口服给予25mg/kg氯唑西林剂量。患者患有轻度至中度CF且病情稳定。CF患者血清浓度显著降低是全身清除率增加78%（P<0.005）和表观分布容积增加38%（P<0.025）的结果。CF患者的生物利用度（0.50）与对照者（0.38）无显著差异，但CF组的变异性更大。静脉给药后，氯唑西林以原形经尿液排泄的比例在对照者（0.644）和CF患者（0.547）中相似。与对照受试者相比，CF患者的平均肾清除率高30%（P<0.10），非肾清除率高144%（P<0.07）。非肾清除率增强解释了在相同体重调整剂量后对照者和CF患者血清浓度之间显示出的大部分差异。数据表明CF患者中氯唑西林的生物转化增强。
