First-dose pharmacokinetics of lithium carbonate in children and adolescents
Authors
Findling, Robert L.Landersdorfer, Cornelia B.
Kafantaris, Vivian
Pavuluri, Mani
McNamara, Nora K.
McClellan, Jon
Frazier, Jean A.
Sikich, Linmarie
Kowatch, Robert
Lingler, Jacqui
Faber, Jon
Taylor-Zapata, Perdita
Jusko, William
UMass Chan Affiliations
Department of PsychiatryDocument Type
Journal ArticlePublication Date
2010-06-10Keywords
Administration, OralAdolescent
Age Factors
Antimanic Agents
Bipolar Disorder
Child
Dose-Response Relationship, Drug
Drug Monitoring
Female
Humans
Lithium Carbonate
Male
*Models, Biological
Nonlinear Dynamics
Randomized Controlled Trials as Topic
Time Factors
Tissue Distribution
Psychiatry
Metadata
Show full item recordAbstract
This study examines the pharmacokinetics of oral doses of lithium carbonate immediate-release capsules after administration of 600 or 900 mg in children and adolescents with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, bipolar I disorder. Lithium plasma concentrations were followed over 48 to 72 hours in 39 subjects (20 male and 19 female subjects; ages, 7-17 years) with mixed or manic episodes enrolled at 7 clinical sites participating in the Collaborative Lithium Trials. Population pharmacokinetic modeling was performed using NONMEM, and influences of patient covariates on pharmacokinetics parameters were examined. The pharmacokinetics of lithium was best described using a 2-compartment model with a lag time and first-order absorption. There was considerable variability in lithium exposures. Lithium clearance related best to fat-free mass. Inclusion of fat-free mass as a covariate reduced the between-subject variability from 52% to 42%. Lithium clearances did not vary systematically with age group, dose, sex, or creatinine clearances. Allometrically scaled clearance and volume of distribution from the population analysis were within the range reported in adults. Single-dose profiles of lithium in young patients with BP-1 show marked variability. Therefore, ongoing serum monitoring is needed during continued therapy. The developed population pharmacokinetic model may be used to predict other dosage regimens, support scaling from adult to pediatric pharmacokinetics, and support the design of future clinical trials.Source
J Clin Psychopharmacol. 2010 Aug;30(4):404-10. Link to article on publisher's siteDOI
10.1097/JCP.0b013e3181e66a62Permanent Link to this Item
http://hdl.handle.net/20.500.14038/45898PubMed ID
20531219Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1097/JCP.0b013e3181e66a62