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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Pharmacokinetic and safety assessments of concurrent administration of risperidone and donepezil.
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Pharmacokinetic and safety assessments of concurrent administration of risperidone and donepezil.

机译：利培酮和多奈哌齐同时给药的药代动力学和安全性评估。

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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.
机译：阿尔茨海默氏病的治疗有时会联合使用药物，因为痴呆症经常与行为症状相关。利培酮和多奈哌齐均通过细胞色素P450 2D6和3A4代谢，从而增加了联合治疗药物相互作用的可能性。这项研究的目的是确定在与多奈哌齐和利培酮同时给药时是否发生显着的药物相互作用。在一项开放式，三方交叉研究中，随机分配24名健康男性接受连续两次，每天两次，每次两次0.5毫克利培酮，每天一次5毫克多奈哌齐或两种药物，连续14天，随后为期21天的洗脱期。定义为利培酮加9-羟基利培酮的比例的利培酮活性部分的AUC和相关的90％置信区间（CIs）的治疗比率（比率= 110.2％; 90％CI = 103.7-117.2）和多奈哌齐（比率= 97.1％; 90％CI = 90.0-103.6）在生物等效性的80％到125％之间。利培酮活性成分（比率= 114.6％; 90％CI = 107.0-122.8）和多奈哌齐（比率= 96.1％; 90％CI = 90.0-102.6）的Cmax和相关90％CI的治疗率也在生物等效性之内范围。因此，单独或组合使用时，利培酮活性成分或多奈哌齐均未发生明显的药代动力学差异。不良事件（主要是头痛，神经质和嗜睡）轻微，在所有治疗组中均具有可比性。结果表明，稳定状态下每天1mg利培酮和5mg每日剂量多奈哌齐之间没有发生临床上有意义的药物相互作用，因此，当两种药物与所研究的剂量方案联合使用时，无需调整剂量。与本研究中检查的年轻健康受试者相比，有必要进行额外的研究以确定老年痴呆患者的相互作用潜力，这些老年痴呆患者可能较慢地消除利培酮和多奈哌齐，因此更容易受到临床药物相互作用的影响。

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