2017年11月
Effect of lipid emulsion infusion on paliperidone pharmacokinetics in the acute overdose rat model: A potential emergency treatment for paliperidone intoxication
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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- 巻
- 109
- 号
- 開始ページ
- 217
- 終了ページ
- 222
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.ejps.2017.08.010
- 出版者・発行元
- ELSEVIER SCIENCE BV
Paliperidone prolongs cardiac repolarization in a concentration-dependent manner. Meanwhile, continuous infusion of intravenous lipid emulsion (ILE) has been established as a detoxification therapy for lipophilic drugs. However, this change in pharmacokinetics of various drugs following ILE administration remains to be clarified. Our objective is to clarify the effect of continuous infusion of ILE on the pharmacokinetics of overdosed paliperidone in rats. Paliperidone (20 mg/kg) was administered orally to free-moving male Wistar rats. Continuous infusion (initial loading dose: 4 ml/kg for 10 min, followed by 4 ml/kg/h for 12 h) of ILE or acetated Ringer's solution (AR) was initiated 30 min after paliperidone administration. Plasma concentration profile of paliperidone was monitored for 12 h after administration. The plasma concentration and tissue/plasma concentration ratios of paliperidone were compared between ILE and AR groups. The rat group infused with ILE showed a higher area under the concentration-time curve (mean [S.D.]: 6102 [900.9] vs. 3407 [992.1] ng h ml(-1), p = 0.02) and longer elimination half-time (t(1/2)) (4.1 [0.9] vs. 2.2 [0.4] h, p= 0.02) compared with the AR group. Tissue/plasma concentration ratios of paliperidone were lower in ILE rats than in AR rats (1.98 [0.70] vs. 3.82 [1.47] in the heart, p= 0.04; 0.28 [0.29] vs. 1.27 [0.58] in the brain, p < 0.001). In conclusion, continuous infusion of ILE would reduce tissue distribution and prolonged the t(1/2) of paliperidone in rats. These results suggest that continuous infusion of ILE has potential as an emergency treatment for acute paliperidone intoxication.
- リンク情報
- ID情報
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- DOI : 10.1016/j.ejps.2017.08.010
- ISSN : 0928-0987
- eISSN : 1879-0720
- PubMed ID : 28821438
- Web of Science ID : WOS:000413325000023