Charbel Fadel, Beata Łebkowska-Wieruszewska, Andrzej Lisowski, Seavchou Laut, Amnart Poapolathep, Mario Giorgi
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Plasma RX concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analysed using ThothPro™ 4.3 software in a non-compartmental approach. Following IV administration, terminal elimination half-life, volume of distribution, and total clearance were 0.35 h, 0.34 L/kg, and 0.68 L/h/kg, respectively. For the PO route, the mean peak plasma concentration was 6.78 μg/mL at 0.50 h. The <i>t</i>1/2<i>λz</i> was very short and significantly different between the IV and PO administrations (0.35 h IV vs. 0.99 h PO), suggesting the occurrence of a flip-flop phenomenon. The Cl values corrected for the <i>F</i>% were significantly different between IV and PO administrations. It might have been a consequence of the longitudinal study design and the altered physiological and environmental conditions after a 4-month washout period. The absolute oral <i>F</i>% computed with the AUC method surpassed 150%, but after normalizing it to <i>t</i>1/2<i>λz</i>, it was 46%. In conclusion, the administration of RX might not be suitable for geese, due to its short <i>t</i>1/2<i>λz</i>.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":"46 6","pages":"413-420"},"PeriodicalIF":1.5000,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Disposition kinetics of robenacoxib following intravenous and oral administration in geese (Anser anser domesticus)\",\"authors\":\"Charbel Fadel, Beata Łebkowska-Wieruszewska, Andrzej Lisowski, Seavchou Laut, Amnart Poapolathep, Mario Giorgi\",\"doi\":\"10.1111/jvp.13398\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Robenacoxib (RX) is a veterinary cyclooxygenase-2 selective inhibitor drug. It has never been tested on birds and is only labelled for use in cats and dogs. The purpose of this study was to assess its pharmacokinetics in geese after single intravenous (IV) and oral (PO) administrations. Four-month healthy female geese (<i>n</i> = 8) were used. Geese were subjected to a two-phase, single-dose (2 mg/kg IV, 4 mg/kg PO), open, longitudinal study design with a four-month washout period between the IV and the PO phases. Blood was collected from the left wing vein to heparinized tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24 h. Plasma RX concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analysed using ThothPro™ 4.3 software in a non-compartmental approach. Following IV administration, terminal elimination half-life, volume of distribution, and total clearance were 0.35 h, 0.34 L/kg, and 0.68 L/h/kg, respectively. For the PO route, the mean peak plasma concentration was 6.78 μg/mL at 0.50 h. The <i>t</i>1/2<i>λz</i> was very short and significantly different between the IV and PO administrations (0.35 h IV vs. 0.99 h PO), suggesting the occurrence of a flip-flop phenomenon. The Cl values corrected for the <i>F</i>% were significantly different between IV and PO administrations. It might have been a consequence of the longitudinal study design and the altered physiological and environmental conditions after a 4-month washout period. The absolute oral <i>F</i>% computed with the AUC method surpassed 150%, but after normalizing it to <i>t</i>1/2<i>λz</i>, it was 46%. 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引用次数: 1
摘要
罗伯那昔布(RX)是一种兽医用环氧合酶-2选择性抑制剂。它从未在鸟类身上进行过测试,只被贴上了用于猫和狗的标签。本研究的目的是评估其在鹅单次静脉(IV)和口服(PO)给药后的药代动力学。四个月健康雌性鹅(n = 8) 使用。鹅接受两阶段、单剂量(2 mg/kg IV,4 mg/kg PO),开放性纵向研究设计,在IV和PO阶段之间有四个月的冲洗期。在0.085(仅用于IV)、0.25、0.5、0.75、1、1.5、2、4、6、8、10和24时,从左翼静脉将血液收集到肝素化管中 h.使用与UV检测器耦合的HPLC测量血浆RX浓度,并使用ThothPro对数据进行药效学分析™ 4.3非分区方法中的软件。静脉注射后,终末消除半衰期、分布体积和总清除率为0.35 h、 0.34 L/kg和0.68 L/h/kg。对于PO途径,平均峰值血浆浓度为6.78 0.50时为μg/mL h.静脉给药和口服给药的t1/2λz非常短,且有显著差异(0.35 h IV与0.99 h PO),表明发生了触发器现象。经F%校正的Cl值在IV和PO给药之间有显著差异。这可能是纵向研究设计以及4个月冲洗期后生理和环境条件改变的结果。用AUC方法计算的绝对口服F%超过150%,但将其归一化为t1/2λz后,为46%。总之,RX的给药可能不适合鹅,因为它的t1/2λz很短。
Disposition kinetics of robenacoxib following intravenous and oral administration in geese (Anser anser domesticus)
Robenacoxib (RX) is a veterinary cyclooxygenase-2 selective inhibitor drug. It has never been tested on birds and is only labelled for use in cats and dogs. The purpose of this study was to assess its pharmacokinetics in geese after single intravenous (IV) and oral (PO) administrations. Four-month healthy female geese (n = 8) were used. Geese were subjected to a two-phase, single-dose (2 mg/kg IV, 4 mg/kg PO), open, longitudinal study design with a four-month washout period between the IV and the PO phases. Blood was collected from the left wing vein to heparinized tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24 h. Plasma RX concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analysed using ThothPro™ 4.3 software in a non-compartmental approach. Following IV administration, terminal elimination half-life, volume of distribution, and total clearance were 0.35 h, 0.34 L/kg, and 0.68 L/h/kg, respectively. For the PO route, the mean peak plasma concentration was 6.78 μg/mL at 0.50 h. The t1/2λz was very short and significantly different between the IV and PO administrations (0.35 h IV vs. 0.99 h PO), suggesting the occurrence of a flip-flop phenomenon. The Cl values corrected for the F% were significantly different between IV and PO administrations. It might have been a consequence of the longitudinal study design and the altered physiological and environmental conditions after a 4-month washout period. The absolute oral F% computed with the AUC method surpassed 150%, but after normalizing it to t1/2λz, it was 46%. In conclusion, the administration of RX might not be suitable for geese, due to its short t1/2λz.
期刊介绍:
The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.