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document
Pharmacokinetic and safety assessments of concurrent administration of risperidone and donepezil . Treatment of Alzheimer 's disease sometimes uses combinations of drugs because dementia is frequently associated with behavioral symptoms . Risperidone and donepezil are both metabolized through cytochrome P450 2D6 and 3A4 , raising the possibility of drug interactions with combination therapy . The objective of this study was to determine whether significant drug interactions occur with concomitant administration of donepezil and risperidone . In an open-label , three-way crossover study , 24 healthy men were randomly assigned to receive 0.5 mg of risperidone twice daily , 5 mg of donepezil once daily , or both drugs for 14 consecutive days , followed by a 21-day washout period . The treatment ratios of AUC and associated 90 % confidence intervals ( CIs ) for risperidone active moiety , defined as risperidone plus 9-hydroxyrisperidone ( ratio = 110.2 % ; 90 % CI = 103.7-117.2 ) , and for donepezil ( ratio = 97.1 % ; 90 % CI = 90.0-103.6 ) were within the 80 % to 125 % of bioequivalence range . The treatment ratios of Cmax and associated 90 % CIs for risperidone active moiety ( ratio = 114.6 % ; 90 % CI = 107.0-122.8 ) and for donepezil ( ratio = 96.1 % ; 90 % CI = 90.0-102.6 ) were also within the bioequivalence range . Therefore , no significant pharmacokinetic differences occurred in either risperidone active moiety or donepezil when given alone or in combination . Adverse events ( predominantly headache , nervousness , and somnolence ) were minor and comparable for all treatment groups . The results indicate that no clinically meaningful drug interactions occurred between risperidone 1 mg daily and donepezil 5 mg daily at steady state , and therefore no dosage adjustment is required when both drugs are combined with the dosage regimen studied . Additional investigations are warranted to determine the potential for interactions in elderly patients with dementia who may eliminate risperidone and donepezil more slowly and thus be more vulnerable to clinical drug interactions than the young healthy subjects examined in this study .
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Intervention_Pharmacological
risperidone
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Intervention_Pharmacological
donepezil .
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Intervention_Pharmacological
Risperidone
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Intervention_Pharmacological
donepezil
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Intervention_Pharmacological
donepezil
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Intervention_Pharmacological
risperidone .
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Intervention_Pharmacological
risperidone
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Intervention_Pharmacological
donepezil
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Outcome_Pain
Pharmacokinetic and safety assessments
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Outcome_Physical
drug interactions
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Outcome_Physical
ratios of AUC
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Outcome_Other
treatment ratios of Cmax and associated 90 % CIs
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Outcome_Other
pharmacokinetic
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Outcome_Other
Adverse events ( predominantly headache , nervousness , and somnolence )
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Outcome_Other
clinically meaningful drug interactions
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Participant_Sample-size
24
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Participant_Condition
healthy
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Participant_Age
young
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Participant_Condition
healthy