Comparative Physicochemical and Pharmacokinetic Properties of Quetiapine and Its Active Metabolite Norquetiapine
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- Kim Dong-Wook
- Department of Pharmaceutical Engineering, Cheongju University
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- Weon Kwon-Yeon
- School of Pharmacy, Catholic University of Daegu
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- Hong Eon-Pyo
- R&D Center, Handok Pharmaceuticals Co., Ltd.
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- Chung Eun Kyoung
- School of Pharmacy, Kyung Hee University
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- Lee Kyung-Tae
- School of Pharmacy, Kyung Hee University
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<p>Quetiapine (QTP) is an atypical antipsychotic drug commonly used to treat several psychiatric disorders and is metabolized into the active metabolite norquetiapine (NQTP). This study was designed to evaluate and compare the physicochemical properties, metabolic stability, brain distribution, and pharmacokinetics of QTP and NQTP. Compared to QTP, NQTP had a higher pKa, solubility, and rat liver microsomal stability, optimal log D and similar log P values. For pharmacokinetic evaluation, QTP and NQTP were administered orally and intravenously to rats at various doses. The plasma QTP and NQTP concentrations in rats were determined by a fully-validated liquid-chromatography tandem mass spectrometry (LC-MS/MS). Over the investigated dosing range, both QTP and NQTP showed linear pharmacokinetics. Following oral administration of the same dose, the area under the concentration–time curve (AUC0–∞) and maximum serum concentration (Cmax) were larger after NQTP administration compared to QTP administration. In addition, NQTP had a greater absolute oral bioavailability compared to QTP (15.6% vs. 0.63%, respectively). The brain-to-plasma concentration ratio was greater after NQTP administration compared to the QTP and NQTP ratios after QTP administration. NQTP administration results in increased systemic exposure and brain distribution compared to QTP administration. Future studies are needed to evaluate the pharmacologic and toxicologic effects of increased NQTP exposures.</p>
収録刊行物
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- CHEMICAL & PHARMACEUTICAL BULLETIN
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CHEMICAL & PHARMACEUTICAL BULLETIN 64 (11), 1546-1554, 2016
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204178566272
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- NII論文ID
- 130005268066
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- NII書誌ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL書誌ID
- 027684487
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- PubMed
- 27803466
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可