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不同禽类物种中卡铂的比较药代动力学及异速生长缩放

Comparative Pharmacokinetics and Allometric Scaling of Carboplatin in Different Avian Species.

作者信息

Antonissen Gunther, Devreese Mathias, De Baere Siegrid, Hellebuyck Tom, Van de Maele Isabel, Rouffaer Lieze, Stemkens Hendrickus J J, De Backer Patrick, Martel An, Croubels Siska

机构信息

Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium; Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

出版信息

PLoS One. 2015 Jul 29;10(7):e0134177. doi: 10.1371/journal.pone.0134177. eCollection 2015.

Abstract

The use of chemotherapeutics as a possible treatment strategy in avian oncology is steadily increasing over the last years. Despite this, literature reports regarding dosing strategies and pharmacokinetic behaviour of chemotherapeutics in avian species are lacking. The aim of the present study was to investigate the pharmacokinetics of carboplatin in a representative species of the order of Galliformes, Anseriformes, Columbiformes and Psittaciformes. Eight chickens, ducks and pigeons and twenty-eight parakeets were administered carboplatin intravenously (5 mg/kg body weight). A specific and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of the free carboplatin in plasma of the four birds species (limit of quantification: 20 ng/mL for chicken and duck, 50 ng/mL for pigeon and 100 ng/mL for parakeets). Non-compartmental pharmacokinetic analysis and allometric scaling demonstrated a significant correlation (R² = 0.9769) between body weight (BW) and elimination half-life (T1/2el). T1/2el ranged from 0.41 h in parakeets (BW: 61 ± 8 g) to 1.16 h chickens (BW: 1909 ± 619 g). T1/2el is a good parameter for dose optimization of carboplatin in other avian species, since also the previously reported T1/2el in cockatoos (average BW: 769 ± 68 g) of 1.00 h corresponds to the results obtained in the present study.

摘要

在过去几年中,将化疗药物作为禽类肿瘤学可能的治疗策略的应用正在稳步增加。尽管如此,关于禽类化疗药物给药策略和药代动力学行为的文献报道却很缺乏。本研究的目的是研究卡铂在鸡形目、雁形目、鸽形目和鹦形目代表性物种中的药代动力学。给8只鸡、鸭和鸽子以及28只长尾小鹦鹉静脉注射卡铂(5毫克/千克体重)。开发并验证了一种特异性和灵敏的液相色谱-串联质谱法,用于定量这四种鸟类血浆中的游离卡铂(定量限:鸡和鸭为20纳克/毫升,鸽子为50纳克/毫升,长尾小鹦鹉为100纳克/毫升)。非房室药代动力学分析和异速生长标度表明体重(BW)与消除半衰期(T1/2el)之间存在显著相关性(R² = 0.9769)。T1/2el范围从长尾小鹦鹉(体重:61±8克)的0.41小时到鸡(体重:1909±619克)的1.16小时。T1/2el是优化其他禽类卡铂剂量的一个良好参数,因为先前报道的凤头鹦鹉(平均体重:769±68克)的T1/2el为1.00小时,与本研究获得的结果相符。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c51/4519271/ca9eb31cae6d/pone.0134177.g001.jpg

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