Abstract
Tz pharmacokinetics were studied in 17 neonates (gestational age (GA) 29-42 weeks; ≤. 34 weeks, n=7) with persistent fetal circulation. Therapy was initiated with 2 mg/kg I.V. loading dose followed by 1 mg/kg/hr I.V. infusion which was increased up to 4 mg/kg/hr based on clinical response. Serial blood samples were obtained post loading dose, during infusion and for 24 hours following termination of infusion. Urine for determination of Tz and creatinine clearance (CrCl) was obtained following attainment of steady-state on the Tz infusion. Tz concentrations were determined by HPLC. The mean ± SD half life (T½), total clearance (Cl), renal clearance (Cl-Ren) and distribution volume (Vd) were 5.9 ± 2.8 hr, 155.3 ± 66.9 ml/min/1.73 m2, 125.5 ± 69.8 ml/min/1.73 m2 and 3.0 ± 1.0 1/kg, respectively. A significant difference (p < 0.01) between neonates ≤ and > 34 weeks GA was observed for Cl, Cl-Ren and T½. Tz Cl and Cl-Ren were found to increase exponentially as a function of GA (Cl vs. GA, Y = 0.08e0.14x, r = 0.83; Cl-Ren vs. GA, Y = 0.03 e0.16x, r=0.81). These parameters were also observed to be significantly correlated to CrCl (Cl vs. CrCl, Y = 6.1X + 1.7, r = 0.87; Cl-Ren vs. CrCl, Y = 5.2X + 0.43, r = 0.89). These results indicate that Tz in neonates is primarily excreted renally by tubular secretion. Tz dosage should be based on the neonate's gestational age and renal function.
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Chow-Tung, E., Fischer, J., Currie, B. et al. 353 FACTORS INFLUENCING TOLAZOLINE (Tz) DISPOSITION IN NEONATES. Pediatr Res 19, 169 (1985). https://doi.org/10.1203/00006450-198504000-00383
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DOI: https://doi.org/10.1203/00006450-198504000-00383