治療精神分裂症的新劑型藥物 - Paliperidone 行政院衛生署桃園療養院藥師鍾欣蓓 鄭淑文 摘要 paliperidoneosmotic controlled release oraldelivery system OROS 24 paliperidone P450 paliperidone schizophrenia osmotic controlled release oral-delivery system,paliperidone 壹 前言 schizophrenia delusion hallucination catatonia dopamine system dopamine extrapyramidal syndrome prolactin serotonin adrenergic extrapyramidal syndrome prolactin Paliperidone osmotic controlled release oral-delivery system OROS 24 paliperidone OROS paliperidone 貳 Paliperidone 作用機轉 Paliperidone risperidone 264 Dec. 31 2010 藥學雜誌第 105 冊 79
臨床藥學 Clinical Pharmacy 9-hydroxyrisperidone D 2 dopamine type 2 receptor 2A serotonin type 2A receptor 5HT 2 APaliperidone D 2 5HT 2 Aolanzapine quetiapine risperidone 3 Paliperidone 1 2 adrenergic H 1 histamine 1 圖一 paliperidone 分子結構 cholinergic muscarinic 1 2 adrenergic 表一比較非典型抗精神病藥物對受體拮抗的強度 / D 2 5HT 2 A 5HT 2 C 1 H 1 Muscarinic Olanzapine ++ + +++ + +++ ++ Quetiapine + ++ + ++ +++ + Risperidone ++ +++ + +++ ++ + Paliperidone ++ +++ + +++ + - 參 滲透泵型控釋系統 (osmotic controlled release oral-delivery system,oros) 劑型介紹 Paliperidone OROS osmotic controlled release oral-delivery system paliperidone OROS 圖二 paliperidone OROS 結構 ➀ ➁ ➂ 80 THE JOURNAL OF TAIWAN PHARMACY Vol.26 No.4 Dec. 31 2010
- Paliperidone 圖三 paliperidone OROS 作用圖 4,5 肆 藥物動力學 paliperidone 28% paliperidone 24 C max 4~5 3-12 mg paliperidone / paliperidone C max AUC Paliperidone 487L 74% paliperidonecyp 2 D 6 CYP 3 A 4 2359% 32% 6-12% 圖四安慰劑及 paliperidone 各種劑量於 PANSS 分數的改善 paliperidonepsp 6 6 伍 臨床試驗 paliperidone PANSS Positive and negative syndrome scale 6 PSP Personal and social performance 圖五 安慰劑及 paliperidone 各種劑量於 PSP 分數的改善 264 Dec. 31 2010 藥學雜誌第 105 冊 81
臨床藥學 Clinical Pharmacy 陸 使用劑量及用法 Paliperidone OROS paliperidone paliperidone risperidone paliperidone Paliperidone OROS 3~12 mg 3 mg 6 mg 5 12 mg paliperidone palmitatepaliperidone palmitate Paliperidone palmitate paliperidone paliperidone palmitate paliperidone palmitate paliperidone palmitate Clcr 50~80 ml/min 6 mg/dayclcr 10~50 ml/min 3 mg/ day 18 4,5 柒 注意事項 Paliperidone paliperidone 17 10 1.6~1.7 QT Paliperidone QTQT QT QTc torsade de pointes / O r t h o s t a t i c hypotensionpaliperidone Neuroleptic Malignant Syndrome NMSNMS hyperpyrexia muscle rigidity creatinine phosphokinase 82 THE JOURNAL OF TAIWAN PHARMACY Vol.26 No.4 Dec. 31 2010
- Paliperidone myoglobinuria rhabdomyolysis Tardive Dyskinesia TDTD Diabetes Mellitus paliperidone OROS PaliperidoneC Paliperidone paliperidone 5 捌 交互作用 Paliperidone cytochrome P-450 paliperidone cytochrome P-450 CYP 1 A 2 CYP 2 A 6 CYP2C 8 / 9 / 10 CYP 2 D 6 CYP 2 E 1 CYP 3 A 4 CYP 3 A 5 1 表二 Paliperidone 之嚴重藥品交互作用 midodrine ajmaline disopyramide procainamide amiodarone bretylium sotalol chlorpromazine prochlorperazine trifluoperazine thioridazine moxifloxacin QT Torsades de points atropine anticholinergic bupropion carbamazepine paliperidone itraconazole paliperidone 4 玖 副作用 paliperidone 2% 3 264 Dec. 31 2010 藥學雜誌第 105 冊 83
臨床藥學 Clinical Pharmacy 表三 以 paliperidone 治療精神分裂症的短期 固定劑量 安慰劑控制試驗中之不良反應 發生率 N=355 3 mg N=127 6 mg N=235 9 mg N=246 12 mg N=242 37 48 47 54 60 心臟疾病 1 2 0 2 1 2 3 1 3 <1 0 2 1 1 <1 7 14 12 12 14 腸胃道疾病 1 1 3 2 2 1 2 3 1 3 <1 0 <1 1 4 全身疾病 1 2 <1 2 2 1 2 1 2 2 神經系統疾病 4 4 3 8 10 4 6 5 4 5 1 1 1 5 4 2 5 2 7 7 12 11 12 14 14 1 2 1 4 3 0 0 <1 2 1 7 6 9 10 11 3 3 3 4 3 血管疾病 1 2 1 2 4 84 THE JOURNAL OF TAIWAN PHARMACY Vol.26 No.4 Dec. 31 2010
- Paliperidone 表四非典型抗精神病藥物之常見副作用比較 QT C Aripiprazole +/- + +/- +/- +/- Clozapine ++++ +/- +/- + ++++ Olanzapine ++++ + +/- + ++++ Paliperidone ++ +++ +++ + ++ Quetiapine ++ +/- +/- + +++ Risperidone ++ +++ +++ + ++ Ziprasidone +/- + + ++ +/- 拾 結論 paliperidone OROS 24 P450 參考資料 : 1. Paliperidone 2008 25 84-89 2. Paliperidone 2007 17 338 3. The Internet Journal of Pharmacology 2009: Volume 7 Number 1. 4. Physician's Desk Reference (P.D.R.), 2009. 5. Micromedex,Inc.Volume 95. 6. Meltzer H, et al. Int J Neuropsychopharmacol 2006; 9 (Suppl 1): S225. 一個頭五個大 264 Dec. 31 2010 藥學雜誌第 105 冊 85
臨床藥學 Clinical Pharmacy The New Dosage Form of A Schizophrenic Drug-paliperidone Hsin-Pei Chung, Shu-Wen Cheng Department of Pharmacy, Taoyuan Mental Hospital,Department of Health Abstract Schizophrenia is a chronic functional mental illness, which needs long-term antipsychotic treatment, and paliperidone is the only antipsychotic drug using osmotic pump technology (osmotic controlled release oral-delivery system, OROS).Paliperidone keeps 24-hour blood levels stable, and patients only need to take one tablet a day. Paliperidone increases patient's medication compliance, and is not metabolized by the cytochrome P450.Accordingly it reduces the drug interaction and provides a new option for patients with schizophrenia. 河床暮色 86 THE JOURNAL OF TAIWAN PHARMACY Vol.26 No.4 Dec. 31 2010