Abstract
To obtain therapeutic “peak” and “trough” concentration of tobra, many CF patients require ↑ dose/kg and ↑ frequency of drug administration. The basis for this is unclear. Tobra clearances after a single 60 mg/m2 IV infusion were studied in 11 stable CF patients with mild to very severe disease to investigate factors which might modify tobra kinetics. The mean age was 16.5 years±3.5; range 10-22, with a mean NIH score of 63±19; range 32-94. The mean % weight for height was 93.1±17.5; range 63.1-122. The lung disease was mild to severe; mean FVC 70.2±23.570 predicted;, range 36-99; mean FEV1 53.4±27.570 predicted; range 17-97. The data could best be described by a two compartment model for drug elimination. Dosing based upon body surface area minimized the effect of malnutrition on attainment of therapeutic levels (mean peak 7.6±1.4mg/l). The half life (T½%) range was 1.24-2.52 hr, the volume of distribution (VD) range was 0.102-0.401 I/kg, the plasma clearance (TPC) range was 43-110 ml/kg/hr and the mean % dose recovered in urine by 24 hours was 78.7±18.5. VD and TPC were ↑ in patients with lower FVC, FEV1 % predicted; those with more severe disease (p's <0.02, strong correlation coefficients). NIH score (contains FVC) also correlated inversely but less strongly (p's< 0.05). Creatinine and inulin clearances correlated only with T½ and VD respectively. Age, nutrition, and PAH clearance did not correlate. Thus, all CF patients are not the same in terms of tobra kinetics. These varied with the disease severity. This suggests that the severity of disease, not just the presence of CF, is the major factor for altered tobra kinetics.
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Macdonald, N., Morris, R. & Peterson, R. DISEASE SEVERITY AS A FACTOR IN ELIMINATION OF TOBRAMYCIN (TOBRA) IN PATIENTS WITH CYSTIC FIBROSIS (CF). Pediatr Res 21 (Suppl 4), 238 (1987). https://doi.org/10.1203/00006450-198704010-00426
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DOI: https://doi.org/10.1203/00006450-198704010-00426