CYP2D6 metabolizer status and atomoxetine dosing in children and adolescents with ADHD

European Neuropsychopharmacology

Volumn 18, Issue 2, 2008, Pages 79-86

  Trzepacz, Paula T ^a,b,c   Williams, David W ^a   Feldman, Peter D ^a   Wrishko, Rebecca E ^a   Witcher, Jennifer W ^a   Buitelaar, Jan K ^d  

^a ELI LILLY AND COMPANY   (United States)

^b UNIVERSITY OF MISSISSIPPI SCHOOL OF MEDICINE   (United States)

^c TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

ADHD; Atomoxetine; Attention deficit hyperactivity disorder; Cytochrome P450 CYP2D6; Genotype

Indexed keywords

ATOMOXETINE; CYTOCHROME P450 2D6;

ADOLESCENT; ARTICLE; ATTENTION DEFICIT DISORDER; BIPOLAR DISORDER; CHILD; CLINICAL TRIAL; CORRELATION ANALYSIS; DRUG BLOOD LEVEL; DRUG DOSE TITRATION; DRUG EFFECT; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; ENZYME ACTIVITY; FEMALE; GENOTYPE; HUMAN; LIVER; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; PULSE RATE; WEIGHT REDUCTION;

ADOLESCENT; ADRENERGIC UPTAKE INHIBITORS; ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY; CHILD; CYTOCHROME P-450 CYP2D6; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION; FEMALE; HUMANS; MALE; PROPYLAMINES; TIME FACTORS;

EID: 37349000292     PISSN: 0924977X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.euroneuro.2007.06.002     Document Type: Article

References (19)

1. Allen A.J., Wernicke J.F., Dunn D., Kratochvil C., West S., Casat C.D., Harder D., Faries D., Laws H.F., Kelsey D.K., Thomasson H., Potter W.Z., and Michelson D. Safety and efficacy of atomoxetine in pediatric CYP2D6 extensive vs. poor metabolizers. Biol. Psychiatry 51 8 suppl (2002) 37S
2. Corman S.L., Fedutes B.A., and Culley C.M. Atomoxetine: the first nonstimulant for the management of attention-deficit/hyperactivity disorder. Am. J. Health-Syst. Pharm. 61 (2004) 2391-2399
3. de Leon J., Armstrong S.C., and Cozza K.L. Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 and CYP450 2C19. Psychosomatics 47 (2006) 75-85
4. Dorado P., Caceres M.C., Pozo-Guisado E., Wong M.L., Licinio J., and Llerena A. Development of a PCR-based strategy for CYP2D6 genotyping including gene multiplication of worldwide potential use. Biotechniques 39 (2005) 571-574
5. Egger T., Dormann H., Ahne G., Pahl A., Runge U., Azaz-Livshits T., Neubert A., Criegee-Rieck M., Gassmann K.G., and Brune K. Cytochrome p450 polymorphisms in geriatric patients: impact on adverse drug reactions-a pilot study. Drugs Aging 22 (2005) 265-272
6. Faries D.E., Yalcin I., Harder D., and Heiligenstein J.H. Validation of the ADHD Rating Scale as a clinician administered and scored instrument. J. Atten. Disord. 5 (2001) 39-47
7. Gardiner S.J., and Begg E.J. Pharmacogenetic testing for drug metabolizing enzymes: is it happening in practice?. Pharmacogenet. Genomics 15 (2005) 365-369
8. 450 proteins and potential utilization in biodegradation. Environ. Health Perspect. 103 suppl 5 (1995) 25-28
9. Guy W. ECDEU Assessment Manual for Psychopharmacology, Revised. Publication ADM 76-338 (1976), United States Department of Health, Education, and Welfare, Bethesda, Md
10. Kaufman J., Birmaher B., Brent D., Rao U., Flynn C., Moreci P., Williamson D., and Ryan N. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL): initial reliability and validity data. J. Am. Acad. Child Adolesc. Psych. 36 (1997) 980-988
11. Kirchheiner J., Bertilsson L., Bruus H., Wolff A., Roots I., and Bauer M. Individualized medicine - implementation of pharmacogenetic diagnostics in antidepressant drug treatment of major depressive disorders. Pharmacopsychiatry 36 suppl 3 (2003) S235-S243
12. Michelson D., Read H.A., Ruff D.D., Witcher J., Zhang S., and McCracken J. CYP2D6 and clinical response to atomoxetine in children and adolescents with ADHD. J. Am. Acad. Child Adolesc. Psych. 46 (2007) 242-251
13. 450 enzyme polymorphisms and adverse drug reactions. Toxicology 192 (2003) 23-32
14. Ring B.J., Gillespie J.S., Eckstein J.A., and Wrighton S.A. Identification of the human cytochromes P450 responsible for atomoxetine metabolism. Drug Metab. Dispos. 30 (2002) 319-323
15. Sauer J.M., Ponsler G.D., Mattiuz E.L., Long A.J., Witcher J.W., Thomasson H.R., and Desante K.A. Disposition and metabolic fate of atomoxetine hydrochloride: the role of CYP2D6 in human disposition and metabolism. Drug Metab. Dispos. 31 (2003) 98-107
16. Sauer J.M., Ring B.J., and Witcher J.W. Clinical pharmacokinetics of atomoxetine. Clin. Pharmacokinet. 44 (2005) 571-590
17. Wernicke J.F., Kratochvil C., Milton D., Dunn D., Spencer T., Heiligenstein J., and Michelson D. Long-term safety of atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder. Presented at: The 155th Annual Meeting of the American Psychiatric Association; May 18-23, 2002; Philadelphia, Pa (2002)
18. Witcher J.W., Long A., Smith B., Sauer J.M., Heiligenstein J., Wilens T., Spencer T., and Biederman J. Atomoxetine pharmacokinetics in children and adolescents with attention deficit hyperactivity disorder. J. Child Adolesc. Psychopharmacol. 13 (2003) 53-63
19. Witcher J.W., Kurtz D., Heathman M., Sauer J.M., and Smith B.P. Population pharmacokinetic analysis of atomoxetine in pediatric patients [abstract]. Clin. Pharmacol. Ther. 75 (2004) 46