Pharmacokinetics of a single oral dose of baclofen in pediatric patients with gastroesophageal reflux disease.

Transient relaxation of the lower esophageal sphincter (TLESR) is the predominant mechanism of gastroesophageal reflux (GER) in adults and children. Baclofen [4-amino-3-(p-chlorophenyl)-butanoic acid], a gamma-aminobutyric acid (GABA)-B receptor agonist used for the management of spasticity, has been recently shown to significantly inhibit GER in healthy adults without any relevant side effects. The objective of this study was to evaluate the pharmacokinetics of baclofen in a pediatric population with GER disease. In an open-label single-dose pharmacokinetic study, eight children with the diagnosis of GER made on clinical grounds received an oral dose of baclofen, 2.5 mg. Blood samples were drawn from an indwelling venous catheter, and urine was collected during a postdose period of 8 hours. The concentration of baclofen in these body fluids was determined using a validated high-performance liquid chromatography (HPLC) method with electrochemical detection after OPA-sulfite derivatization. Pharmacokinetic data were analyzed using the nonlinear regression program Scientist. Serum concentration-time curves could be best described using a two-compartment open model with a lag time. Mean plasma clearance (Cl) was 315.9 mL/h/kg; volume of distribution (Vd) was 2.58 L/kg; and half-life (T(1/2)beta) was 5.10 hours. No side effects were noted. As half-lives were comparable with those found in adult studies, the risk for accumulation seems not greater in children than in adults. Body composition can have a strong influence on the Vd of baclofen and, therefore, on the dose needed to obtain therapeutic plasma levels. Dosing according to clearly defined age groups with the help of therapeutic drug monitoring seems preferable. In view of the negative correlation between body weight and Vd, dosing according to body weight using adult pharmacokinetic data does not seem an effective way for using baclofen in children.

Respiratory distress syndrome in Curaçao. Conventional versus surfactant treatment.

The aim of this study was to determine the incidence of Respiratory Distress Syndrome (RDS) and to evaluate the efficacy of surfactant treatment at the Neonatal Intensive Care Unit (NICU) at the St Elisabeth Hospital, Curaçao, Netherlands, Antilles. This was a retrospective cohort study of 86 infants, with moderate to severe RDS, out of 877 newborns admitted to the NICU between 1991 and 1998. Results of conventional RDS treatment between 1991 and 1994 (n = 54, group 1) were compared to results of treatment between 1994 and 1998 (n = 32, group 2) with surfactant and increased prenatal steroids. The incidence of RDS in group 1 was 12%, and 7.5% in group 2. Use of prenatal steroids increased from 7.3% (group 1) to 47% in group 2 (p < 0.05). Twenty-five infants died, 17 (31.5%) in group 1 and 8 (25%) in group 2. The complication most frequently found in both study groups was Bronchopulmonary Dysplasia (BPD): sixteen infants (30%) in group 1 and 9 infants (28%) in the surfactant-treated group. BPD was significantly associated with time on the ventilator in both groups (p < 0.05). We found no cases (0%) of Retinopathy of Prematurity (ROP) in group 1, and 3 cases (9%, p < 0.05) in group 2. We found no differences in other complications between group 1 and 2. The mean time between birth and the first surfactant treatment in group 2 was more than nine hours. Surfactant rescue treatment in combination with prenatal steroids results in lower incidence of RDS and in lower mortality than conventional RDS treatment in this study. The increased incidence of ROP in the surfactant-treated group was probably the result of better detection. BPD and other complications remained unchanged. Earlier surfactant administration is suggested to reduce mortality and morbidity in the future.

Respiratory distress syndrome in Curaçao. Conventional versus surfactant treatment

The aim of this study was to determine the incidence of Respiratory Distress Syndrome (RDS) and to evaluate the efficacy of surfactant treatment at the Neonatal Intensive Care Unit (NICU) at the St Elisabeth Hospital, Curaçao, Netherlands, Antilles. This was a retrospective cohort study of 86 infants, with moderate to severe RDS, out of 877 newborns admitted to the NICU between 1991 and 1998. Results of conventional RDS treatment between 1991 and 1994 (n = 54, group 1) were compared to results of treatment between 1994 and 1998 (n = 32, group 2) with surfactant and increased prenatal steroids. The incidence of RDS in group 1 was 12, and 7.5 in group 2. Use of prenatal steroids increased from 7.3 (group 1) to 47 in group 2 (p < 0.05). Twenty-five infants died, 17 (31.5) in group 1 and 8 (25) in group 2. The complication most frequently found in both study groups was Bronchopulmonary Dysplasia (BPD): sixteen infants (30) in group 1 and 9 infants (28) in the surfactant-treated group. BPD was significantly associated with time on the ventilator in both groups (p < 0.05). We found no cases (0) of Retinopathy of Prematurity (ROP) in group 1, and 3 cases (9, p < 0.05) in group 2. We found no differences in other complications between group 1 and 2. The mean time between birth and the first surfactant treatment in group 2 was more than nine hours. Surfactant rescue treatment in combination with prenatal steroids results in lower incidence of RDS and in lower mortality than conventional RDS treatment in this study. The increased incidence of ROP in the surfactant-treated group was probably the result of better detection. BPD and other complications remained unchanged. Earlier surfactant administration is suggested to reduce mortality and morbidity in the future.