Fluorine magnetic resonance spectroscopy measurement of brain fluvoxamine and fluoxetine in pediatric patients treated for pervasive developmental disorders.
OBJECTIVE
Pediatric populations, including those with autistic disorder or other pervasive developmental disorders, increasingly are being prescribed selective serotonin reuptake inhibitors (SSRIs). Little is known about the age-related brain pharmacokinetics of SSRIs; there is a lack of data regarding optimal dosing of medications for children. The authors used fluorine magnetic resonance spectroscopy ((19)F MRS) to evaluate age effects on whole-brain concentrations of fluvoxamine and fluoxetine in children taking SSRIs.


METHODS
Twenty-one pediatric subjects with diagnoses of autistic disorder or other pervasive developmental disorders, 6-15 years old and stabilized with a consistent dose of fluvoxamine or fluoxetine, were recruited for the study; 16 successfully completed the imaging protocol. Whole-brain drug levels in this group were compared to similarly acquired data from 28 adults.


RESULTS
A significant relationship between dose and brain drug concentration was observed for both drugs across the age range studied. Brain fluvoxamine concentration in the children was lower, consistent with a lower dose/body mass drug prescription; when brain concentration was adjusted for dose/mass, age effects were no longer significant. Brain fluoxetine concentration was similar between age groups; no significant age effects on brain fluoxetine drug levels remained after adjustment for dose/mass. Observations of brain fluoxetine bioavailability and elimination half-life also were similar between age groups.


CONCLUSIONS
These findings suggest that fluvoxamine or fluoxetine prescriptions adjusted for dose/mass are an acceptable treatment approach for medicating children with autistic disorder or other pervasive developmental disorders. It must be determined whether these findings can be generalized to other pediatric populations.
Strauss
Wayne L
WL
Center on Human Development and Disability, University of Washington, Seattle, 98105-6099, USA.
Unis
Alan S
AS
Cowan
Charles
C
Dawson
Geraldine
G
Dager
Stephen R
SR
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001321:Autistic Disorder / Q000188:drug therapy / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy* / Q000378:metabolism; D003866:Depressive Disorder / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005461:Fluorine; D005473:Fluoxetine / Q000032:analysis* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016666:Fluvoxamine / Q000032:analysis* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000706:statistics & numerical data; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy / Q000378:metabolism; D016584:Panic Disorder / Q000188:drug therapy / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000032:analysis* / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D005461:Fluorine; D005473:Fluoxetine; D016666:Fluvoxamine; D017367:Selective Serotonin Reuptake Inhibitors