The pharmacokinetics of mianserin suppositories for rectal administration in dogs and healthy volunteers: a pilot study.
The pharmacokinetics of mianserin suppositories for rectal administration in dogs and healthy volunteers: a pilot study.
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DOI：
10.1186/s40780-016-0046-7
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发表时间：
2016
影响因子：
1
通讯作者：
Yamamoto T
中科院分区：
文献类型：
--
作者：
Nawata S;Kohyama N;Uchida N;Numazawa S;Ohbayashi M;Kobayashi Y;Iwata M;Nakajima T;Saito H;Izuka A;Yamamoto T
我们配制了米安色林栓剂用于治疗谵妄，并通过测量犬和健康志愿者的血浆药物浓度来评估其药代动力学。使用Tetramide®片剂和Witepsol H-15作为栓剂基质，通过熔融技术制备米安色林栓剂。根据伦理委员会的批准，在3只比格犬和3只健康成年雄性犬中评价了该30 mg米安色林制剂的药代动力学。使用气相色谱-质谱法测定血浆米安色林水平。在犬中，米安色林的最大血浆浓度（Cmax）为1.3 ± 0.4 ng/mL，达到Cmax的时间（tmax）为5.5 ± 4.3 h，0 - 24 h的血浆浓度-时间曲线下面积（AUC 0 -24）为18.9 ± 1.9 h·ng/mL。在人体中，Cmax为14.6 ± 6.3 ng/mL，tmax为8 h，AUC 0 -24为266 ± 103 h·ng/mL。本研究描述了米安色林栓剂在犬和人中的药代动力学特征。与口服给药相比，栓剂产生的Cmax较低，tmax延迟，但AUC 0 -24值相当。有必要确定产生足够的米安色林血药浓度的适当剂量，以确保有效和安全的临床使用。UMIN000013853。
We formulated mianserin suppositories for the treatment of delirium and evaluated their pharmacokinetics by measuring plasma drug concentrations in dogs and healthy human volunteers. Mianserin suppositories were prepared by a melting technique using Tetramide® tablets and Witepsol H-15 as the suppository base. Pharmacokinetics of this 30-mg mianserin preparation were evaluated in three beagle dogs and three healthy adult males, in line with ethics committee approval. Plasma mianserin levels were determined using gas chromatography–mass spectrometry. In dogs, the maximum plasma mianserin concentration (Cmax) was 1.3 ± 0.4 ng/mL, the time to Cmax (tmax) was 5.5 ± 4.3 h, and the area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) was 18.9 ± 1.9 h・ng/mL. In humans, the Cmax was 14.6 ± 6.3 ng/mL, the tmax was 8 h, and the AUC0-24 was 266 ± 103 h・ng/mL. The current study characterized the pharmacokinetics of mianserin suppositories in dogs and humans. As compared to oral administration, the suppositories produced a lower Cmax and a delayed tmax, although AUC0-24 values were comparable. It will be necessary to identify an appropriate dose that produces an adequate plasma mianserin concentration for effective and safe clinical use. UMIN000013853.