Fluoxetine pharmacokinetics in pediatric patients

被引:48
作者
Wilens, TE
Cohen, L
Biederman, J
Abrams, A
Neft, D
Faird, N
Sinha, V
机构
[1] Harvard Univ, Pediat Psychopharmacol Unit, Massachusetts Gen Hosp, Sch Med,Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA
[2] Lilly Lab Clin Res, Indianapolis, IN USA
关键词
D O I
10.1097/00004714-200212000-00006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The objective of this study was to evaluate the pharmacokinetic profile of fluoxetine (FLX) and its major metabolite, norfluoxetine (NORFLX), in children and adolescent patients undergoing psychiatric treatment. Twenty-one pediatric subjects-10 children (6-12 years) and 11 adolescents (13-18 years)-were administered 20 mg FLX for 60 days, with sparse blood samples taken throughout the open-label study. Subjects contributed 168 plasma concentrations. Pharmacokinetic parameters were estimated using a mixed effects nonlinear model. Mean steady-state FLX and NORFLX of 12 7 ng/mL and 151 ng/mL, respectively, were achieved in children and adolescents after 4 weeks of treatment, with high between-patient variability. FLX was 2-fold higher and NORFLX was 1.7-fold higher in children relative to adolescents; however, when normalized to body weight, FLX and NORFLX were similar for both age groups. Age, body weight, body mass index, and body surface area, modeled independently as continuous variables, significantly improved the population pharmacokinetic model when evaluated as patient factors. Body weight was the covariate retained in the final model. In conclusion, children have 2-fold higher FLX and NORFLX relative to adolescents that appear to be related to indices of body size. The accumulation profile and steady-state concentrations in adolescents appear similar to those in adults.
引用
收藏
页码:568 / 575
页数:8
相关论文
共 37 条
[1]   Sertraline treatment of children and adolescents with obsessive-compulsive disorder or depression: Pharmacokinetics, tolerability and efficacy [J].
Alderman, J ;
Wolkow, R ;
Chung, M ;
Johnston, HF .
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY, 1998, 37 (04) :386-394
[2]   CLINICAL PHARMACOKINETICS OF FLUOXETINE [J].
ALTAMURA, AC ;
MORO, AR ;
PERCUDANI, M .
CLINICAL PHARMACOKINETICS, 1994, 26 (03) :201-214
[3]  
ANDERSON JC, 1987, ARCH GEN PSYCHIAT, V44, P69
[4]   FLUOXETINE KINETICS AND PROTEIN-BINDING IN NORMAL AND IMPAIRED RENAL-FUNCTION [J].
ARONOFF, GR ;
BERGSTROM, RF ;
POTTRATZ, ST ;
SLOAN, RS ;
WOLEN, RL ;
LEMBERGER, L .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1984, 36 (01) :138-144
[5]  
BEASLEY CM, 1990, PSYCHOPHARMACOL BULL, V26, P18
[6]  
BELANGER B, 1995, BIOMETRICS, V52, P158
[7]   THE EFFECTS OF RENAL AND HEPATIC-DISEASE ON THE PHARMACOKINETICS, RENAL TOLERANCE, AND RISK-BENEFIT PROFILE OF FLUOXETINE [J].
BERGSTROM, RF ;
BEASLEY, CM ;
LEVY, NB ;
BLUMENFIELD, M ;
LEMBERGER, L .
INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY, 1993, 8 (04) :261-266
[8]   CLINICAL-PHARMACOLOGY AND PHARMACOKINETICS OF FLUOXETINE - A REVIEW [J].
BERGSTROM, RF ;
LEMBERGER, L ;
FARID, NA ;
WOLEN, RL .
BRITISH JOURNAL OF PSYCHIATRY, 1988, 153 :47-50
[9]   PATTERNS OF DIAGNOSTIC COMORBIDITY IN A COMMUNITY SAMPLE OF CHILDREN AGED 9 THROUGH 16 YEARS [J].
BIRD, HR ;
GOULD, MS ;
STAGHEZZA, BM .
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY, 1993, 32 (02) :361-368
[10]   Desipramine clearance in children and adolescents: Absence of effect of development and gender [J].
Cohen, LG ;
Biederman, J ;
Wilens, TE ;
Spencer, TJ ;
Mick, E ;
Faraone, SV ;
Prince, J ;
Flood, JG .
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY, 1999, 38 (01) :79-85