臺灣博碩士論文加值系統

某些他汀類的藥物(simvastatin，lovastatin，atorvastatin)是經細胞色素P450 3A4 (CYP3A4)代謝。抑制CYP3A4的藥物，包括某些鈣離子阻斷劑，可能會因為藥物交互作用增加他汀類藥物的濃度。如果同時開立經CYP3A4代謝的他汀類藥物與抑制CYP3A4的鈣離子阻斷劑可能會增加不良反應的風險，例如造成急性腎損傷。本研究是一個全人口資料庫研究，分析1997到2011健保資料庫的病人資料。共有32801個病人同時服用他汀類藥物與抑制CYP3A4的鈣離子阻斷劑（amlodipine，diltiazem，felodipine，nicardipine，nifedipine，verapamil)。這些病人分成兩組，一組是服用經CYP3A4代謝的他汀類藥物(lovastatin，simvastatin，atorvastatin)，另一組是服用不經CYP3A4代謝的他汀類藥物(fluvastatin，rosuvastatin，pitavastatin)。這兩組依據年齡、性別與察爾森共病症指標一比一配對，然後觀察藥物同時開立後九十天內的不良反應。
在這個研究中，同時服用經CYP3A4代謝的他汀類藥物與抑制CYP3A4的鈣離子阻斷劑的病人共有5857位。比較病人服用經CYP3A4代謝的他汀類藥物，與病人服用不經CYP3A4代謝的他汀類藥物，兩組的共病與降血壓藥物都沒有差異。病人服用經CYP3A4代謝的他汀類藥物，比起病人服用不經CYP3A4代謝的他汀類藥物，有較高的急性腎損傷的風險 (危險比2.12；95%信賴區間1.35-3.35)，較高的高血鉀風險 (危險比2.94;95%信賴區間1.36–6.35)，較高的心肌梗塞風險 (危險比1.55;95%信賴區間1.16-2.07)，與急性缺血性中風的風險 (危險比1.35;95%信賴區間 1.08–1.68)。
這個全國世代研究證明，同時開立經CYP3A4代謝的他汀類藥物與抑制CYP3A4的鈣離子阻斷劑可能增加不良反應的風險。當同時開立經CYP3A4代謝的他汀類藥物與抑制CYP3A4的鈣離子阻斷劑時，考慮潛在不良反應的風險是很重要的。

Some statins (simvastatin, lovastatin, and atorvastatin) are metabolized by cytochrome P450s 3A4 (CYP3A4). Inhibitors of CYP3A4 including some calcium channel blockers (CCB) might increase statin blood concentration, owing to drug-drug interactions. Risk of adverse events such as acute kidney injury might occur following the coprescription of CYP3A4-metabolized statins and CCBs that inhibit CYP3A4.
This was a population-based cohort study. The study analyzed data of patients treated between 1997 and 2011, retrieved from Taiwan’s National Health Insurance database. We enrolled 32801 patients who received coprescription of statins and CCBs that inhibit CYP3A4 (amlodipine, diltiazem, felodipine nicardipine, nifedipine, and verapamil). These patients were divided into 2 groups, according to whether they had received CYP3A4-metabolized statins (lovastatin, simvastatin, and atorvastatin) or non-CYP3A4-metabolized statins (fluvastatin, rosuvastatin, and pitavastatin). These two groups were 1:1 matched by age, gender, and Carlson comorbidity index. All outcomes were assessed within 90 days following drug coprescription.
In this study, 5857 patients received coprescription of CYP3A4-metabolized statins and CCBs that inhibit CYP3A4. There were no differences in comorbidity or use of antihypertensive drugs between patients who received CYP3A4-metabolized statins and those who received non-CYP3A4-metabolized statins. Patients who received CYP3A4-metabolized statins had significantly higher risk of acute kidney injury [adjusted odds ratio (OR) = 2.12; 95% CI = 1.35–3.35], hyperkalemia (adjusted OR = 2.94; 95% CI = 1.36–6.35), acute myocardial infarction (adjusted OR = 1.55; 95% CI = 1.16–2.07) and acute ischemic stroke (adjusted OR = 1.35; 95% CI = 1.08–1.68) than those who received non-CYP3A4-metabolized statins.
This nationwide cohort study demonstrated the increased risk of adverse events following the coprescription of CYP3A4-metabolized statins and CCBs that inhibit CYP3A4. Therefore, it is important to take into account the potential adverse events while co-prescribing CYP3A4-metabolized statins and CCBs that inhibit CYP3A4.

Chapter 1 Introduction
Chapter 2 Literature review
2-1 CYP3A4
2-2 Drug interactions
Chapter 3 Hypothesis
Chapter 4 Materials and Methods
4-1 Data Collection
4-2 Study Subject Selection Process
4-3 Measurements of Outcomes
4-4 Statistical Analysis
Chapter 5 Results
5-1 Study Population
5-2 Baseline Aharacteristics
5-3 Risk of Adverse Events after Coprescription
5-4 Relationships Between Adverse Events and Baseline
Characteristics
5-5 Risk of Adverse Events During 90 days Prior to
Coprescription and 91–180 Days After Coprescription
Chapter 6 Discussion
Chapter 7 Conclusion
Chapter 8 Prospects
Reference

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