Dataset Information

Population pharmacokinetics of oral baclofen in pediatric patients with cerebral palsy.

ABSTRACT:

Objective

To characterize the population pharmacokinetics (PK) of oral baclofen and assess impact of patient-specific covariates in children with cerebral palsy (CP) in order to support its clinical use.

Subjects design

Children (2-17 years of age) with CP received a dose of titrated oral baclofen from 2.5 mg 3 times a day to a maximum tolerated dose of up to 20 mg 4 times a day. PK sampling followed titration of 10-12 weeks. Serial R- and S-baclofen plasma concentrations were measured for up to 16 hours in 49 subjects. Population PK modeling was performed using NONMEM 7.1 (ICON PLC; Ellicott City, Maryland).

Results

R- and S-baclofen showed identical concentration-time profiles. Both baclofen enantiomers exhibited linear and dose/kg-proportional PK, and no sex differences were observed. Average baclofen terminal half-life was 4.5 hours. A 2-compartment PK model with linear elimination and transit absorption steps adequately described concentration-time profiles of both baclofen enantiomers. The mean population estimate of apparent clearance/F was 0.273 L/h/kg with 33.4% inter-individual variability (IIV), and the apparent volume of distribution (Vss/F) was 1.16 L/kg with 43.9% IIV. Delayed absorption was expressed by a mean transit time of 0.389 hours with 83.7% IIV. Body weight, a possible genetic factor, and age were determinants of apparent clearance in these children.

Conclusion

The PK of oral baclofen exhibited dose-proportionality and were adequately described by a 2-compartment model. Our population PK findings suggest that baclofen dosage can be based on body weight (2 mg/kg per day) and the current baclofen dose escalation strategy is appropriate in the treatment of children with CP older than 2 years of age.

SUBMITTER: He Y

PROVIDER: S-EPMC3992203 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Publications

Population pharmacokinetics of oral baclofen in pediatric patients with cerebral palsy.

He Yang Y Brunstrom-Hernandez Janice E JE Thio Liu Lin LL Lackey Shellie S Gaebler-Spira Deborah D Kuroda Maxine M MM Stashinko Elaine E Hoon Alexander H AH Vargus-Adams Jilda J Stevenson Richard D RD Lowenhaupt Stephanie S McLaughlin John F JF Christensen Ana A Dosa Nienke P NP Butler Maureen M Schwabe Aloysia A Lopez Christina C Roge Desiree D Kennedy Diane D Tilton Ann A Krach Linda E LE Lewandowski Andrew A Dai Hongying H Gaedigk Andrea A Leeder J Steven JS Jusko William J WJ

The Journal of pediatrics 20140305 5

<h4>Objective</h4>To characterize the population pharmacokinetics (PK) of oral baclofen and assess impact of patient-specific covariates in children with cerebral palsy (CP) in order to support its clinical use.<h4>Subjects design</h4>Children (2-17 years of age) with CP received a dose of titrated oral baclofen from 2.5 mg 3 times a day to a maximum tolerated dose of up to 20 mg 4 times a day. PK sampling followed titration of 10-12 weeks. Serial R- and S-baclofen plasma concentrations were mea ...[more]

PMID: 24607242

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Dataset Information

Population pharmacokinetics of oral baclofen in pediatric patients with cerebral palsy.

Objective

Subjects design

Results

Conclusion

Publications

Population pharmacokinetics of oral baclofen in pediatric patients with cerebral palsy.

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