Abstract
Parents, investigators and ethical committess must bear the responsibility for ensuring that the potential risks of research in the neonatal age group are acceptable and that the study will yield useful information. Pharmacokinetic studies require that multiple blood samples be taken. Because of potential hypovolemia and anemia in neonates, especially if pre term, it is essential that the least invasive study designs be used. This study aimed to determine the least number of samples that are required to obtain accurate pharmacokinetic parameters and dosing schedules by the analysis of 2 pharmacokinetic studies.
Neonates treated with ceftazidime or netilmicin who had had at least 6 samples taken after the first dose or during steady state were studied. 12 concentration time curves from 10 infants on ceftazidime and 20 from 15 infants on netilmicin were used. Half life (T1/2), systemic clearance (Cl) and Volume of distribution (Vd) were calculated using all the available points and then recalculated using 2 points (the post dose and last), 3 points (first. last and mid time point), and 4 points.
Significant differences were found between results using 2 points and results using all the points for CI and Vd for both drugs. When 3 points were used only Vd for netilmicin was different, and no differences were apparent when 4 points were used.
Using parameters obtained from 2 points, dosage would be underestimated by a mean of 15% (range 35% underdosage to 24% overdosage) for ceftazidime and by a mean of 11% for netilmicin (range 31% under to 14% overdosage). The corresponding figures for dosage based on 3 points were a mean underdosing of 1% (range 10% under to 14% overdosing) for ceftazidime and a mean underdosing of 5% for netilmicin (range 24% under to 7% overdosing).
We conclude that 3 samples taken between doses may be all that are required for the estimation of pharmacokinetic parameters sufficiently accurate for practical purposes in neonates.
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Long, D., Koren, G. & James, A. ETHICAL CONSIDERATIONS IN PHARMACOKINETIC STUDIES IN NEONATES. Pediatr Res 21 (Suppl 4), 238 (1987). https://doi.org/10.1203/00006450-198704010-00425
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DOI: https://doi.org/10.1203/00006450-198704010-00425