TY - JOUR
T1 - Pharmacokinetics of a single oral dose of baclofen in pediatric patients with gastroesophageal reflux disease
AU - Wiersma, H. E.
AU - van Boxtel, C. J.
AU - Butter, J. J.
AU - van Aalderen, W. M. C.
AU - Omari, T.
AU - Benninga, M. A.
PY - 2003
Y1 - 2003
N2 - 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 (T1/2beta) 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
AB - 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 (T1/2beta) 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
U2 - https://doi.org/10.1097/00007691-200302000-00014
DO - https://doi.org/10.1097/00007691-200302000-00014
M3 - Article
C2 - 12548151
SN - 0163-4356
VL - 25
SP - 93
EP - 98
JO - Therapeutic drug monitoring
JF - Therapeutic drug monitoring
IS - 1
ER -