Aranda J V, Varvarigou A, Beharry K, Bansal R, Bardin C, Modanlou H, Papageorgiou A, Chemtob S
Department of Pediatrics, McGill University, Montreal, Canada.
Acta Paediatr. 1997 Mar;86(3):289-93. doi: 10.1111/j.1651-2227.1997.tb08892.x.
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-1, plasma clearance was 2.06 +/- 0.33 ml/kg/h and plasma concentration (Cp) at 1 h was 180.6 +/- 11.1 mg/l. 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/l and 113.6 +/- 58.2 mg/l, 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.
为预防早产儿脑室内出血和动脉导管未闭，对布洛芬（IBU）在早产儿体内的消除、处置及蛋白结合情况进行了研究。对出生后3小时内静脉注射赖氨酸布洛芬（10mg/kg负荷剂量）的21例早产儿（平均出生体重=944.7g，范围：575 - 1450g；胎龄：26.8周，范围：22 - 31周）的动力学特征进行了研究。给药后0、1、3、6、12、24、48和72小时采集血样（0.3ml/样本），采用高效液相色谱法（HPLC）测定IBU。动力学分析假设单室开放模型适用，并根据时间浓度曲线下非模型依赖面积（AUC）进行计算。数据（均值±标准误）显示，表观分布容积（AVd）为62.1±3.9ml/kg，血浆β半衰期（t1/2β）为30.5±4.2小时，消除速率常数（Kel）为0.032±0.004h-1，血浆清除率为2.06±0.33ml/kg/h，给药后1小时血浆浓度（Cp）为180.6±11.1mg/l。胎龄和出生体重与药物消除无关。在10例新生儿中，第2天和第3天每日一次5mg/kg的IBU维持剂量产生的平均Cp分别为116.6±54.5mg/l和113.6±58.2mg/l。通过超滤和毛细管电泳进行的蛋白结合研究表明，与成人血浆蛋白相比，足月脐带血浆中IBU的结合百分比显著较低（94.98±0.39%，n = 26）（成人血浆蛋白均值±标准误=98.73±0.31%，n = 8，p<0.0001）。与成人及大龄儿童的数据相比，新生儿中IBU的消除明显延长，蛋白结合率略低。因此，研究和临床治疗方案应进行调整，以考虑药物处置的降低，确保安全有效的治疗。
