Abstract
Results: Among the 105 subjects enrolled, 72% were female and 36% were African American. Subjects had a mean age of 79.6 years. The population used a mean of eight medications per day (prescription and nonprescription). The CYP2D6 activity score frequencies were 0 (3.8%), 0.5 (4.8%), 1.0 (36.2%), 1.5-2.0 (51.4%), and 2.0 (3.8%). Nineteen subjects (18.1%) used a medication considered a strong or moderate inhibitor of CYP2D6, and eight subjects (7.6%) used a medication considered a strong or moderate inhibitor of CYP3A4/5. In total, 28.6% of the study population was predicted to have reduced activity of the CYP2D6 or CYP3A4/5 enzymes due to either genetic variants or concomitant medications.
Conclusion: Both pharmacogenetic variants and concurrent drug therapies that are predicted to alter the pharmacokinetics of AChEIs should be evaluated in older adults with AD. Pharmacogenetic and drug-interaction data may help personalize AD therapy and increase adherence by improving tolerability.
Objective: To determine the frequency of pharmacogenomic variants and concurrent medications that may alter the efficacy and tolerability of acetylcholinesterase inhibitors (AChEIs).
Materials and methods: A multisite cross-sectional study was carried out across four memory care practices in the greater Indianapolis area. Participants were adults aged 65 years and older with a diagnosis of probable or possible Alzheimer’s disease (AD) (n=105). Blood samples and self-reported medication data were collected. Since two of the three AChEIs are metabolized by cytochrome P450 (CYP)-2D6, we determined the frequency of functional genetic variants in the CYP2D6 gene and calculated their predicted CYP2D6-activity scores. Concurrent medication data were collected from self-reported medication surveys, and their predicted effect on the pharmacokinetics of AChEIs was determined based on their known effects on CYP2D6 and CYP3A4/5 enzyme activities.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 269-275 |
| Number of pages | 7 |
| Journal | Clinical interventions in aging |
| Volume | 10 |
| DOIs | |
| State | Published - Jan 13 2015 |
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Keywords
- Acetylcholinesterase inhibitor
- Dementia
- Pharmacogenomics
ASJC Scopus subject areas
- Geriatrics and Gerontology
Cite this
Characterization of hepatic enzyme activity in older adults with dementia : Potential impact on personalizing pharmacotherapy. / Campbell, Noll L.; Skaar, Todd C.; Perkins, Anthony J.; Gao, Sujuan; Li, Lang; Khan, Babar A.; Boustani, Malaz A.
In: Clinical interventions in aging, Vol. 10, 13.01.2015, p. 269-275.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of hepatic enzyme activity in older adults with dementia
T2 - Potential impact on personalizing pharmacotherapy
AU - Campbell, Noll L.
AU - Skaar, Todd C.
AU - Perkins, Anthony J.
AU - Gao, Sujuan
AU - Li, Lang
AU - Khan, Babar A.
AU - Boustani, Malaz A.
PY - 2015/1/13
Y1 - 2015/1/13
N2 - Results: Among the 105 subjects enrolled, 72% were female and 36% were African American. Subjects had a mean age of 79.6 years. The population used a mean of eight medications per day (prescription and nonprescription). The CYP2D6 activity score frequencies were 0 (3.8%), 0.5 (4.8%), 1.0 (36.2%), 1.5-2.0 (51.4%), and 2.0 (3.8%). Nineteen subjects (18.1%) used a medication considered a strong or moderate inhibitor of CYP2D6, and eight subjects (7.6%) used a medication considered a strong or moderate inhibitor of CYP3A4/5. In total, 28.6% of the study population was predicted to have reduced activity of the CYP2D6 or CYP3A4/5 enzymes due to either genetic variants or concomitant medications.Conclusion: Both pharmacogenetic variants and concurrent drug therapies that are predicted to alter the pharmacokinetics of AChEIs should be evaluated in older adults with AD. Pharmacogenetic and drug-interaction data may help personalize AD therapy and increase adherence by improving tolerability.Objective: To determine the frequency of pharmacogenomic variants and concurrent medications that may alter the efficacy and tolerability of acetylcholinesterase inhibitors (AChEIs).Materials and methods: A multisite cross-sectional study was carried out across four memory care practices in the greater Indianapolis area. Participants were adults aged 65 years and older with a diagnosis of probable or possible Alzheimer’s disease (AD) (n=105). Blood samples and self-reported medication data were collected. Since two of the three AChEIs are metabolized by cytochrome P450 (CYP)-2D6, we determined the frequency of functional genetic variants in the CYP2D6 gene and calculated their predicted CYP2D6-activity scores. Concurrent medication data were collected from self-reported medication surveys, and their predicted effect on the pharmacokinetics of AChEIs was determined based on their known effects on CYP2D6 and CYP3A4/5 enzyme activities.
AB - Results: Among the 105 subjects enrolled, 72% were female and 36% were African American. Subjects had a mean age of 79.6 years. The population used a mean of eight medications per day (prescription and nonprescription). The CYP2D6 activity score frequencies were 0 (3.8%), 0.5 (4.8%), 1.0 (36.2%), 1.5-2.0 (51.4%), and 2.0 (3.8%). Nineteen subjects (18.1%) used a medication considered a strong or moderate inhibitor of CYP2D6, and eight subjects (7.6%) used a medication considered a strong or moderate inhibitor of CYP3A4/5. In total, 28.6% of the study population was predicted to have reduced activity of the CYP2D6 or CYP3A4/5 enzymes due to either genetic variants or concomitant medications.Conclusion: Both pharmacogenetic variants and concurrent drug therapies that are predicted to alter the pharmacokinetics of AChEIs should be evaluated in older adults with AD. Pharmacogenetic and drug-interaction data may help personalize AD therapy and increase adherence by improving tolerability.Objective: To determine the frequency of pharmacogenomic variants and concurrent medications that may alter the efficacy and tolerability of acetylcholinesterase inhibitors (AChEIs).Materials and methods: A multisite cross-sectional study was carried out across four memory care practices in the greater Indianapolis area. Participants were adults aged 65 years and older with a diagnosis of probable or possible Alzheimer’s disease (AD) (n=105). Blood samples and self-reported medication data were collected. Since two of the three AChEIs are metabolized by cytochrome P450 (CYP)-2D6, we determined the frequency of functional genetic variants in the CYP2D6 gene and calculated their predicted CYP2D6-activity scores. Concurrent medication data were collected from self-reported medication surveys, and their predicted effect on the pharmacokinetics of AChEIs was determined based on their known effects on CYP2D6 and CYP3A4/5 enzyme activities.
KW - Acetylcholinesterase inhibitor
KW - Dementia
KW - Pharmacogenomics
UR - http://www.scopus.com/inward/record.url?scp=84921457216&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84921457216&partnerID=8YFLogxK
U2 - 10.2147/CIA.S65980
DO - 10.2147/CIA.S65980
M3 - Article
C2 - 25609939
AN - SCOPUS:84921457216
VL - 10
SP - 269
EP - 275
JO - Clinical Interventions in Aging
JF - Clinical Interventions in Aging
SN - 1176-9092
ER -