Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant

Wiley - Tập 86 Số 3 - Trang 289-293 - 1997
J. Aranda1, Anastasia Varvarigou1, Kay D. Beharry2,3, Ranju Bansal1, Claudette Bardin1, Houchang D. Modanlou2,3, Apostolos Papageorgiou1, Sylvain Chemtob1
1University of California, Irvine Long Beach, California
2Departments of Pediatrics, Pharmacology & Therapeutics, McGill University and the Department of Neonatology, Jewish General Hospital, Lady Davis Institute for Medical Research, Montreal Canada
3Long Beach Memorial Medical Center

Tóm tắt

The elimination, disposition and protein binding of ibuprofen (IBU) in premature infants were studied for use in the prevention of intraventricular hemorrhage and closure of patent ductus arteriosus. The kinetic profile of i.v. IBU 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: 22–31 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 liquid chromatography (HPLC). Kinetic analyses assumed applicability of one open‐compartment model and calculations from the model‐independent 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 t1/2 beta was 30.5 ± 4.2 h, elimination rate constant (kel) was 0.032 ± 0.004 h‐1plasma clearance was 2.06 ± 0.33 ml/kg/h and plasma concentration (Cp) at 1 h was 180.6 ±11.1 mg/1. Gestational age and birthweight were not related to drug elimination. In 10 neonates, IBU maintenance dose of 5 mg/kg once daily on days 2 and 3 generated mean Cp of 116.6 ± 54.5 mg/1 and 113.6 ± 58.2mg/1, respectively. Protein binding by ultrafiltration and capillary electrophoresis showed that the percentage bound IBU was significantly lower in full term cord plasma (94.98 ± 0.39%, n= 26) compared to adult plasma protein (mean ± SE = 98.73 ± 0.31%, n= 8, p < 0.0001). Compared to data from adults and older children, IBU elimination is markedly prolonged in neonates and protein binding is slightly lower. Thus, investigational and clinical therapeutic regimens should be adjusted to account for decreased drug disposition to ensure safe and effective therapy.

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Tài liệu tham khảo

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Wiley

Tập 86 Số 3

289-293

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