Abstract
T doses in current clinical use were derived without pharmacokinetic studies in infants. We developed a chemically-specific assay for T and measured its pharmacokinetics following pulse and infusion doses (n=12) and its concentration changes during infusion doses in 8 infants. T half-life correlated with urine output from 0.40-2.35 ml/kg/hr (R=0.77). The overall T beta (β) averaged 0.0033±0.0023 (±SD, n=12) with distribution volume of 1495±630 ml/kg in 6 infants who received single pulse doses. T infusions between 1.0 and 5.8 mg/kg/hr for 10.8-101.5 hrs produced progressive accumulation of T in all patients. The highest infant T concentration (16.4 μg/ml) approached lethal, cardiotoxic levels in animals (21.8 μg/ml). Current T infusion doses exceed neonatal clearance of T, even with normal urine output. Using the infants' average β and Vdβ, the T infusion dose to maintain a constant plasma T concentration can be estimated as 0.2 mg/kg/hr for each 1.0 mg/kg loading dose. Current infusion doses of T are much higher than those predicted by neonatal T pharmacokinetics, may account for accumulation of T in neonates, and may lead to adverse effects. Oliguria during T infusion may require further decreases in dose. Intermittent pulse doses of T may be safer than continuous infusions.
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Ward, R., Kending, J., Daniel, C. et al. TOLAZOLINE (T) DOSE ADJUSTMENTS BASED UPON NEONATAL PHARMACOKINETICS. Pediatr Res 18 (Suppl 4), 354 (1984). https://doi.org/10.1203/00006450-198404001-01567
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DOI: https://doi.org/10.1203/00006450-198404001-01567
