Abstract
In 15 patients (8 to 22 years of age) with cystic fibrosis (CF) the plasma concentration time profile of tobramycin was carefully monitored by sampling plasma 15 times during 8 hours. The obtained data were well fitted by a two-compartment open model. It appeared that the concentration-time curves and some of the derived pharmacokinetic parameters were clearly age-dependent [1], T½α, T½β and the area under the concentration-time curve per unit of dose were inversely correlated with age and body weight. Using the experience obtained in such patients a single tobramycin dosage scheme for CF patients of all age groups was formulated, intending not to overshoot a plasma level of 2 μg/ml tobramycin at the end of the dosage interval, whereas the period in which a plasma level less than 1 μg/ml existed would be minimal. We were of opinion that by such a scheme CF patients would be treated optimally, while avoiding toxicity. This scheme is adapted to the pharmacokinetic behaviour of individual patients by measuring two points of the concentration-time curve of tobramycin in a patient and subsequently adjusting the dosage interval to individual needs. The therapeutic gain obtained with the scheme is the subject of part II of this study.
[1] Pharmacokinetics of tobramycin in patients with cystic fibrosis; implications for the dosing interval. Chest 88 (1985) 260-264.
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Driessen, O., Horrevorts, A., Kerrebijn, K. et al. 79 DOSING TOBRAMYCIN IN CHILDREN WITH CYSTIC FIBROSIS USING SERUM CONCENTRATIONS. I. PHARMACOKINETICS. Pediatr Res 20, 1046 (1986). https://doi.org/10.1203/00006450-198610000-00133
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DOI: https://doi.org/10.1203/00006450-198610000-00133