Tags

Type your tag names separated by a space and hit enter

CYP2D6 predicted metabolizer status and safety in adult patients with attention-deficit hyperactivity disorder participating in a large placebo-controlled atomoxetine maintenance of response clinical trial.
J Clin Pharmacol. 2015 Oct; 55(10):1167-74.JC

Abstract

Atomoxetine, which is indicated for treatment of attention-deficit hyperactivity disorder (ADHD), is predominantly metabolized by genetically polymorphic cytochrome P450 2D6 (CYP2D6). Based on identified CYP2D6 genotypes, individuals can be categorized into 4 phenotypic metabolizer groups as ultrarapid, extensive, intermediate, and poor. Previous studies have focused on observed differences between poor and extensive metabolizers, but it is not well understood whether the safety profile of intermediate metabolizers differs from that of ultrarapid and extensive metabolizers. This study compared safety and tolerability among the different CYP2D6 metabolizer groups in the 12-week open-label phase of an atomoxetine study in adult patients with ADHD. Genotyping identified 1039 patients as extensive/ultrarapid metabolizers, 780 patients as intermediate metabolizers, and 117 patients as poor metabolizers. Common (≥5% frequency) treatment-emergent adverse events did not significantly differ between extensive/ultrarapid and intermediate metabolizers (odds ratios were <2.0 or >0.5). Poor metabolizers had higher frequencies of dry mouth, erectile dysfunction, hyperhidrosis, insomnia, and urinary retention compared with the other metabolizer groups. There were no significant differences between extensive/ultrarapid and intermediate metabolizers in changes from baseline in vital signs. These results suggest that data from CYP2D6 intermediate and extensive/ultrarapid metabolizers can be combined when considering safety analyses related to atomoxetine.

Authors+Show Affiliations

Eli Lilly and Company, Indianapolis, IN, USA.Eli Lilly and Company, Indianapolis, IN, USA.BioStatSolutions, Inc., Frederick, MD, USA.Eli Lilly and Company, Indianapolis, IN, USA.Eli Lilly Japan KK, Kobe, Japan.Eli Lilly and Company, Indianapolis, IN, USA.Eli Lilly and Company, Indianapolis, IN, USA.Eli Lilly and Company, Indianapolis, IN, USA.

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25919121

Citation

Fijal, Bonnie A., et al. "CYP2D6 Predicted Metabolizer Status and Safety in Adult Patients With Attention-deficit Hyperactivity Disorder Participating in a Large Placebo-controlled Atomoxetine Maintenance of Response Clinical Trial." Journal of Clinical Pharmacology, vol. 55, no. 10, 2015, pp. 1167-74.
Fijal BA, Guo Y, Li SG, et al. CYP2D6 predicted metabolizer status and safety in adult patients with attention-deficit hyperactivity disorder participating in a large placebo-controlled atomoxetine maintenance of response clinical trial. J Clin Pharmacol. 2015;55(10):1167-74.
Fijal, B. A., Guo, Y., Li, S. G., Ahl, J., Goto, T., Tanaka, Y., Nisenbaum, L. K., & Upadhyaya, H. P. (2015). CYP2D6 predicted metabolizer status and safety in adult patients with attention-deficit hyperactivity disorder participating in a large placebo-controlled atomoxetine maintenance of response clinical trial. Journal of Clinical Pharmacology, 55(10), 1167-74. https://doi.org/10.1002/jcph.530
Fijal BA, et al. CYP2D6 Predicted Metabolizer Status and Safety in Adult Patients With Attention-deficit Hyperactivity Disorder Participating in a Large Placebo-controlled Atomoxetine Maintenance of Response Clinical Trial. J Clin Pharmacol. 2015;55(10):1167-74. PubMed PMID: 25919121.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CYP2D6 predicted metabolizer status and safety in adult patients with attention-deficit hyperactivity disorder participating in a large placebo-controlled atomoxetine maintenance of response clinical trial. AU - Fijal,Bonnie A, AU - Guo,Yingying, AU - Li,Si G, AU - Ahl,Jonna, AU - Goto,Taro, AU - Tanaka,Yoko, AU - Nisenbaum,Laura K, AU - Upadhyaya,Himanshu P, Y1 - 2015/06/14/ PY - 2014/12/17/received PY - 2015/04/22/accepted PY - 2015/4/29/entrez PY - 2015/4/29/pubmed PY - 2016/6/23/medline KW - ADHD KW - CYP2D6 metabolizer KW - atomoxetine SP - 1167 EP - 74 JF - Journal of clinical pharmacology JO - J Clin Pharmacol VL - 55 IS - 10 N2 - Atomoxetine, which is indicated for treatment of attention-deficit hyperactivity disorder (ADHD), is predominantly metabolized by genetically polymorphic cytochrome P450 2D6 (CYP2D6). Based on identified CYP2D6 genotypes, individuals can be categorized into 4 phenotypic metabolizer groups as ultrarapid, extensive, intermediate, and poor. Previous studies have focused on observed differences between poor and extensive metabolizers, but it is not well understood whether the safety profile of intermediate metabolizers differs from that of ultrarapid and extensive metabolizers. This study compared safety and tolerability among the different CYP2D6 metabolizer groups in the 12-week open-label phase of an atomoxetine study in adult patients with ADHD. Genotyping identified 1039 patients as extensive/ultrarapid metabolizers, 780 patients as intermediate metabolizers, and 117 patients as poor metabolizers. Common (≥5% frequency) treatment-emergent adverse events did not significantly differ between extensive/ultrarapid and intermediate metabolizers (odds ratios were <2.0 or >0.5). Poor metabolizers had higher frequencies of dry mouth, erectile dysfunction, hyperhidrosis, insomnia, and urinary retention compared with the other metabolizer groups. There were no significant differences between extensive/ultrarapid and intermediate metabolizers in changes from baseline in vital signs. These results suggest that data from CYP2D6 intermediate and extensive/ultrarapid metabolizers can be combined when considering safety analyses related to atomoxetine. SN - 1552-4604 UR - https://www.unboundmedicine.com/medline/citation/25919121/CYP2D6_predicted_metabolizer_status_and_safety_in_adult_patients_with_attention_deficit_hyperactivity_disorder_participating_in_a_large_placebo_controlled_atomoxetine_maintenance_of_response_clinical_trial_ L2 - https://doi.org/10.1002/jcph.530 DB - PRIME DP - Unbound Medicine ER -