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经电渗法和直肠给药治疗不明病因脑膜脑炎犬的阿糖胞苷生物利用度。

The bioavailability of cytarabine in dogs with meningoencephalitis of unknown etiology through iontophoresis and rectal delivery.

机构信息

NC State University Veterinary Hospital, 1052 William Moore Drive, Raleigh, NC, 27607, USA.

Veterinary Medical Center of Long Island, 75 Sunrise Highway, West Islip, NY, 11795-2033, USA.

出版信息

Open Vet J. 2021 Jan-Mar;11(1):36-38. doi: 10.4314/ovj.v11i1.6. Epub 2021 Jan 17.

DOI:10.4314/ovj.v11i1.6
PMID:33898281
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8057209/
Abstract

BACKGROUND

Cytarabine (CA) is used to treat dogs with meningoencephalitis of unknown etiology (MUE) by subcutaneous or intravenous administration.

AIM

The objective was to investigate transdermal iontophoresis and rectal administration as alternative routes of CA delivery.

METHODS

Two client-owned dogs with MUE were studied. The ActivaPatch® IONTOGO™ 12.0 iontophoresis drug delivery system delivered 200 mg/m2 CA transdermally. Blood samples were collected by sparse sampling technique after initiation of the device. At another visit, 100 mg/m2 CA was administered rectally. Blood samples were collected by sparse sampling technique after administration. Plasma CA concentrations were measured by high-pressure liquid chromatography.

RESULTS

The concentration of plasma CA after transdermal and rectal administration was below the limits of quantification (0.1 μg/ml) in all samples suggesting inadequate bioavailability with transdermal and rectal administration.

CONCLUSION

Transdermal and rectal CA administration are not reasonable alternative routes of delivery.

摘要

背景

阿糖胞苷(CA)通过皮下或静脉给药用于治疗病因不明的脑膜脑炎(MUE)的犬。

目的

本研究旨在探索经皮离子电渗和直肠给药作为 CA 递药的替代途径。

方法

对 2 只患有 MUE 的患犬进行研究。使用 ActivaPatch® IONTOGO™ 12.0 经皮离子电渗给药系统经皮给予 200mg/m2 CA。在装置启动后通过稀疏采样技术采集血样。在另一次就诊时,经直肠给予 100mg/m2 CA。给药后通过稀疏采样技术采集血样。通过高压液相色谱法测量 CA 的血浆浓度。

结果

所有样本中经皮和直肠给予 CA 后的 CA 血浆浓度均低于定量下限(0.1μg/ml),提示经皮和直肠给予 CA 的生物利用度不足。

结论

经皮和直肠给予 CA 不是合理的递药替代途径。

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本文引用的文献

1
The pharmacokinetics of cytarabine administered subcutaneously, combined with prednisone, in dogs with meningoencephalomyelitis of unknown etiology.皮下注射阿糖胞苷联合泼尼松在病因不明的脑膜脑脊髓炎犬中的药代动力学。
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2
Effect of a constant rate infusion of cytosine arabinoside on mortality in dogs with meningoencephalitis of unknown origin.持续静脉输注阿糖胞苷对不明原因脑膜脑炎犬死亡率的影响。
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Prodrug strategies for enhancing the percutaneous absorption of drugs.提高药物经皮吸收的前药策略。
Molecules. 2014 Dec 12;19(12):20780-807. doi: 10.3390/molecules191220780.
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Site specific rectal drug administration in man with an osmotic system: influence on "first-pass" elimination of lidocaine.经渗透系统行男性直肠局部给药:对利多卡因“首过”消除的影响。
Pharm Res. 1984 May;1(3):129-34. doi: 10.1023/A:1016380104424.
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The pharmacokinetics of cytarabine in dogs when administered via subcutaneous and continuous intravenous infusion routes.阿糖胞苷经皮下和持续静脉输注途径给药时在犬体内的药代动力学。
J Vet Pharmacol Ther. 2013 Aug;36(4):408-11. doi: 10.1111/jvp.12008. Epub 2012 Sep 3.
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Clinical findings and treatment of non-infectious meningoencephalomyelitis in dogs: a systematic review of 457 published cases from 1962 to 2008.临床发现和犬非感染性脑膜脑炎的治疗:1962 年至 2008 年 457 例已发表病例的系统综述。
Vet J. 2010 Jun;184(3):290-7. doi: 10.1016/j.tvjl.2009.03.031. Epub 2009 May 1.
7
Procarbazine as adjunctive therapy for treatment of dogs with presumptive antemortem diagnosis of granulomatous meningoencephalomyelitis: 21 cases (1998-2004).丙卡巴肼作为辅助治疗用于对生前疑似肉芽肿性脑膜脑脊髓炎的犬进行治疗:21例病例(1998 - 2004年)
J Vet Intern Med. 2007 Jan-Feb;21(1):100-6. doi: 10.1892/0891-6640(2007)21[100:paatft]2.0.co;2.
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Iontophoresis - an approach for controlled drug delivery: a review.离子电渗疗法——一种可控药物递送方法:综述
Curr Drug Deliv. 2007 Jan;4(1):1-10. doi: 10.2174/1567201810704010001.
9
Combined cytosine arabinoside and prednisone therapy for meningoencephalitis of unknown aetiology in 10 dogs.联合使用阿糖胞苷和泼尼松治疗10只病因不明的犬脑膜脑炎。
J Small Anim Pract. 2006 Oct;47(10):588-95. doi: 10.1111/j.1748-5827.2006.00172.x.
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Am J Vet Res. 1995 Dec;56(12):1629-36.