PHARMACOKINETICS AND PROTEIN-BINDING OF INTRAVENOUS IBUPROFEN IN THE PREMATURE NEWBORN-INFANT

The elimination, disposition and protein binding of ibuprofen (IBU) in premature infants were studied for use in the prevention of intravent ricular hemorrhage and closure of patent ductus arteriosus. The kineti c profile of i.v. IBV lysine (10 mg/kg bolus) given within the first 3 h after birth was studied in 21 premature neonates (mean birthweight = 944.7 g, range: 575-1450 g; gestational age: 26.8 weeks, range: 22-3 1 weeks). Blood samples (0.3 ml/sample) were obtained at time 0 and at 1, 3, 6, 12, 24, 48, and 72 h post-dose for IBU by high-performance l iquid chromatography (HPLC). Kinetic analyses assumed applicability of one open-compartment model and calculations from the model-independen t areas under the time concentration curve (AUC). Data (mean +/- SEM) show that apparent volume of distribution (AVd) was 62.1 +/- 3.9 ml/kg , plasma t(1/2) beta was 30.5 +/- 4.2 h, elimination rate constant (k( el)) was 0.032 +/- 0.004 h(-1), plasma clearance was 2.06 +/- 0.33 ml/ kg/h and plasma concentration (Cp) at Ih was 180.6 +/- 11.1 mg/l. Gest ational age and birthweight were not related to drug elimination. In 1 0 neonates, IBU maintenance dose of 5 mg/kg once daily on days 2 and 3 generated mean Cp of 116.6 +/- 54.5 mg/l and 113.6 +/- 58.2 mg/l, res pectively. Protein binding by ultrafiltration and capillary electropho resis showed that the percentage bound IBU was significantly lower in full term cord plasma (94.98 +/- 0.39%, n = 26) compared to adult plas ma protein (mean +/- SE = 98.73 +/- 0.31%, n = 8, p < 0.0001). Compare d to data from adults and older children, IBU elimination is markedly prolonged in neonates and protein binding is slightly lower. Thus, inv estigational and clinical therapeutic regimens should be adjusted to a ccount for decreased drug disposition to ensure safe and effective the rapy.