PEDIATRICS Vol. 77 No. 3 March 1986, pp. 307-315
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Oliguria and Tolazoline Pharmacokinetics in the Newborn

Robert M. Ward MD1, Catherine H. Daniel BS1, James W. Kendig MD1, and Mary A. Wood BS1

1 The Departments of Pediatrics and Pharmacology, The Milton S. Hershey Medical Center, Pennsylvania State University, Hershey

Tolazoline treatment of neonates has been reported since 1965. Dosages increased from pulse doses of 1 to 2 mg/kg to continuous infusions of 10 mg/kg.h before neonatal plasma tolazoline concentrations were measured. We developed a microassay for tolazoline and determined neonatal distribution volume, 1.61 ± 0.21 L/ kg, and disposition rate constant (beta), 0.0027 ± 0.005 min-1 (mean ± SEM). Half-life (y) ranged from 1.47 to 41.25 (median =4.43) hours and correlated inversely with urine output (x); y (h) = -0.46 + 7.63/x (mL/kg.h), r = .61, P < .05. The highest plasma tolazoline concentration in a neonate was 20.3 mg/L. Lethal tolazoline concentrations in lambs ranged from 21.8 to 56.8 mg/L. Initial tolazoline concentrations during infusions and after 1- to 2-mg/kg pulse doses ranged from 0.35 to 2.3 mg/L and PaO2 increased ge15 mm Hg in 64% of 14 treatments. The average neonatal pharmacokinetics predict that each 1 mg of tolazoline HC1 per kilogram pulse dose will increase the plasma concentration of tolazoline base by 0.5 mg/L. The plasma concentration should remain constant with infusion dose increments of 0.16 mg of tolazoline HC1 per kilogram per hour for every 1.0-mg/kg loading dose. Tolazoline dose requirements for specific patients will vary, especially with renal dysfunction. Reduced tolazoline doses were used to treat two patients, concentrations remained constant, and PaO2 was maintained. Tolazoline doses derived from neonatal kinetics are less than current infusion doses and may avoid high concentrations.

Key Words: newborn • tolazoline • pharmacokinetics • oliguria • drug toxicity

Submitted on November 19, 1984
Accepted on May 31, 1985


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