Abstract
PURPOSE: Pentoxifylline (PTX) may decrease coronary artery damage in Kawasaki Disease (KD) by inhibiting TNF-α production. This study evaluated the safety and pharmacokinetics (PK) of a new pediatric oral syrup preparation of PTX as an adjunct to intravenous immunoglobulin and aspirin in the treatment of KD in children. METHODS: Six patients were enrolled/cohort (Cohorts A, B, C, and D- 10, 15, 20, and 25 mg/kg/day; divided TID). TNF-α levels (Days 1 and 6) were evaluated by ELISA. Six PK sera collected around the first dose were measured by HPLC and evaluated by non-compartmental analysis for PTX and its active metabolite (M-I). RESULTS: The most common adverse events were vomiting and fever, each reported in 5 of 18 patients. No toxicities were dose-related. For Cohorts A and B, the mean age ± SD was 33 ± 21 months. The median baseline TNF-α level was 9.51 pg/mL. Of 8 patients with day 6 TNF-α levels, six had an average decrease in TNF-α of 28%. The PTX mean areas under the plasma concentration versus time curve (AUC, a measure of drug exposure) were 559 (range, 216-1886) and 1786 (range, 286-9199) ng*hr/mL, and the M-I mean AUCs were 950 (range, 363-1826) and 3162 (range, 1069-12055) ng*hr/mL for Cohorts A and B, respectively. The overall apparent clearances (Cl/F) were 5.9 (range, 1.7-15.9) and 2.8 (range, 0.9-17.5) L/hr/kg. The M-I/PTX ratio was 1.7 and 1.8 in Cohorts A and B, respectively. No evidence of accumulation or saturation of absorption was noted. CONCLUSIONS: PTX was well tolerated. Gastrointestinal symptoms may have been due to high dose aspirin, PTX, or the combination of the two medications. The pharmacokinetic parameters were highly variable and similar to those seen in other populations. After analysis of Cohorts C and D, we will determine the optimal dose of PTX in KD.
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Burns, J., Best, B., Chou, E. et al. Pharmacokinetic and Safety Evaluation of a Pediatric Formulation of Pentoxifylline for Treatment of Acute Kawasaki Disease. Pediatr Res 53, 182 (2003). https://doi.org/10.1203/00006450-200301000-00171
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DOI: https://doi.org/10.1203/00006450-200301000-00171
