Hedman A, Adan-Abdi Y, Alvan G, Strandvik B, Arvidsson A
Department of Clinical Pharmacology, Karolinska Institutet, Huddinge University Hospital, Sweden.
Clin Pharmacokinet. 1988 Jul;15(1):57-65. doi: 10.2165/00003088-198815010-00005.
The renal handling of ceftazidime was studied in 8 patients with cystic fibrosis and 10 healthy controls. The renal clearance of ceftazidime (CLRcz) was measured after an intravenous single dose and during low and high plasma concentration steady-state infusions. The glomerular filtration rate (GFR) was simultaneously estimated by inulin clearance (CL inul). The average CLRcz (mean +/- SD) was higher in cystic fibrosis patients (125 +/- 20 ml/min/1.73 m2) than in healthy controls (100 +/- 9 ml/min/1.73 m2) [p less than 0.005]. Also CL inul (mean +/- SD) was increased in cystic fibrosis patients (132 +/- 30 ml/min/1.73 m2) compared with healthy controls (103 +/- 8 ml/min/1.73 m2) [p less than 0.02]. The mean renal clearance ratios of ceftazidime to inulin were close to unity after both the single dose and low and high dose steady-state infusions both in cystic fibrosis patients and in controls. These findings suggest that the glomerular filtration rate is the principal determinant of the elimination rate of ceftazidime. However, in all cystic fibrosis patients with a CL inul exceeding 125 ml/min/1.73 m2 the clearance ratio was below unity, indicating tubular reabsorption of ceftazidime occurs in these individuals. The results demonstrate a higher but also more variable GFR in cystic fibrosis patients (74 to 174 ml/min/1.73 m2), resulting in increased and accordingly variable ability to eliminate ceftazidime in cystic fibrosis. However, these pharmacokinetic changes are not large enough to call for special dosage considerations for ceftazidime in cystic fibrosis.
对8例囊性纤维化患者和10名健康对照者进行了头孢他啶的肾脏处理研究。静脉单次给药后以及在低血浆浓度和高血浆浓度稳态输注期间，测量了头孢他啶的肾脏清除率（CLRcz）。通过菊粉清除率（CL inul）同时估算肾小球滤过率（GFR）。囊性纤维化患者的平均CLRcz（均值±标准差）（125±20 ml/min/1.73 m2）高于健康对照者（100±9 ml/min/1.73 m2）[p<0.005]。与健康对照者（103±8 ml/min/1.73 m2）相比，囊性纤维化患者的CL inul（均值±标准差）也有所增加（132±30 ml/min/1.73 m2）[p<0.02]。在囊性纤维化患者和对照者中，单次给药以及低剂量和高剂量稳态输注后，头孢他啶与菊粉的平均肾脏清除率比值均接近1。这些发现表明肾小球滤过率是头孢他啶消除率的主要决定因素。然而，在所有CL inul超过125 ml/min/1.73 m2的囊性纤维化患者中，清除率比值低于1，表明这些个体中发生了头孢他啶的肾小管重吸收。结果表明，囊性纤维化患者的GFR更高且更具变异性（74至174 ml/min/1.73 m2），导致囊性纤维化患者消除头孢他啶的能力增强且相应变异性增加。然而，这些药代动力学变化不足以要求对囊性纤维化患者的头孢他啶进行特殊剂量考虑。
