Influence of the Glomerular Filtration Rate on Renal Clearance of Ceftazidime in Cystic Fibrosis

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Abstract
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 (CLinul). The average CLRcz (mean ± SD) was higher in cystic fibrosis patients (125 ± 20 ml/min/1.73m2) than in healthy controls (100 ± 9 ml/min/1.73m2) [p < 0.005]. Also CLinul (mean ± SD) was increased in cystic fibrosis patients (132 ± 30 ml/min/1.73m2) compared with healthy controls (103 ± 8 ml/min/1.73m2) [p < 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 CLinul exceeding 125 ml/min/1.73m2 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/1.73m2), 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.