Pharmacokinetic profile of a single intramuscular or oral dose of meloxicam in red kangaroos (Osphranter rufus).

IF 1.4 3区 农林科学 Q2 VETERINARY SCIENCES American journal of veterinary research Pub Date : 2025-03-21 Print Date: 2025-06-01 DOI:10.2460/ajvr.24.10.0326
Ellis M Wright, Louden Wright, Sherry Cox, Heather Schwartz
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引用次数: 0

Abstract

Objective: Determine pharmacokinetic parameters of meloxicam in red kangaroos following a single IM or PO dose.

Methods: In the spring of 2024, following a pilot study to determine the appropriate dosage, a managed population of clinically healthy adult or subadult red kangaroos at the Nashville Zoo received a 0.2-mg/kg dose of meloxicam, IM or PO. Four additional kangaroos received a 0.2-mg/kg dose of meloxicam, IV, to establish bioavailability. Blood samples were obtained under manual restraint over 48 hours, using a sparse sampling method. Plasma meloxicam concentration was determined using HPLC. Plasma meloxicam time-concentration profiles were established using a non-compartmental pharmacokinetic analysis.

Results: 15 kangaroos were included in this study. Eight kangaroos were assigned to the IM group, and 8 were assigned to the PO group. Pharmacokinetic parameters were time to the maximum observed plasma concentration (tmax) = 0.5 hours, maximum plasma concentration (Cmax) = 1.071 μg/mL, terminal half-life (t½) = 13.03 hours, elimination rate constant (λz) = 0.05 1/h, area under the plasma concentration-versus-time curve from time 0 to last point (AUC0-last) = 11.643 h·μg/mL, area under the plasma concentration-versus-time curve from time 0 to infinity (AUC0-∞) = 12.460 h·μg/mL, bioavailability = 129%, and apparent volume of distribution after extravascular administration (V/F) = 234 mL/kg, and tmax = 6 hours, Cmax = 0.445 μg/mL, t1/2 = 9.90 hours, λz = 0.07 1/h, AUC0-last = 6.666 h·μg/mL, AUC0-∞ = 7.023 h·μg/mL, bioavailability = 73%, and V/F = 557 mL/kg for the IM and PO groups, respectively. One kangaroo collapsed and died approximately 15 minutes following administration of an IV dose of meloxicam. Necropsy revealed intracranial hemorrhage.

Conclusions: The Cmax and t1/2 of meloxicam were greater in the IM group than the PO group. When dosed IM, plasma meloxicam concentrations reached levels reported to be therapeutic in other species, while this was inconsistently achieved with PO dosing.

Clinical relevance: IM meloxicam may offer advantages to PO dosing due to the greater Cmax and longer t1/2. Nonsteroidal anti-inflammatory drugs are known to decrease platelet function, and it is unknown if red kangaroos are at increased risk for hemorrhage following the administration of meloxicam compared to other species.

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红袋鼠(Osphranter rufus)单次肌注或口服剂量美洛昔康的药代动力学特征。
目的:测定美洛昔康单次IM或PO给药后在红袋鼠体内的药动学参数。方法:在2024年春季,在一项确定适当剂量的试点研究之后,纳什维尔动物园的一群临床健康的成年或亚成年红袋鼠接受了0.2 mg/kg剂量的美洛西康、IM或PO。另外4只袋鼠接受了0.2 mg/kg剂量的美洛昔康IV,以确定生物利用度。血液样本在人工约束下采集超过48小时,采用稀疏采样方法。采用高效液相色谱法测定血浆美洛昔康浓度。采用非室室药代动力学分析建立血浆美洛昔康时间-浓度谱。结果:本研究共纳入15只袋鼠。8只袋鼠被分配到IM组,8只袋鼠被分配到PO组。药代动力学参数为:至最大观察血药浓度时间(tmax) = 0.5 h,最大血药浓度(Cmax) = 1.071 μg/mL,终末半衰期(t½)= 13.03 h,消除速率常数(λz) = 0.05 1/h, 0时刻至最后一点血药浓度-时间曲线下面积(AUC0-last) = 11.643 h·μg/mL, 0时刻至无穷远点血药浓度-时间曲线下面积(AUC0-∞)= 12.460 h·μg/mL,生物利用度= 129%,IM组和PO组血管外表观分布容积(V/F) = 234 mL/kg, tmax = 6 h, Cmax = 0.445 μg/mL, t1/2 = 9.90 h, λz = 0.07 1/h, AUC0-last = 6.666 h·μg/mL, AUC0-∞= 7.023 h·μg/mL,生物利用度= 73%,V/F = 557 mL/kg。一只袋鼠在静脉注射美洛昔康大约15分钟后倒地死亡。尸检显示颅内出血。结论:IM组美洛昔康的Cmax和t1/2均高于PO组。当给药IM时,血浆美洛昔康浓度达到其他物种报道的治疗水平,而这与给药PO不一致。临床相关性:IM美洛昔康由于Cmax更大,t1/2更长,可能比PO给药有优势。已知非甾体类抗炎药会降低血小板功能,并且尚不清楚与其他物种相比,红袋鼠在服用美洛昔康后出血的风险是否增加。
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来源期刊
CiteScore
1.70
自引率
10.00%
发文量
186
审稿时长
3 months
期刊介绍: The American Journal of Veterinary Research supports the collaborative exchange of information between researchers and clinicians by publishing novel research findings that bridge the gulf between basic research and clinical practice or that help to translate laboratory research and preclinical studies to the development of clinical trials and clinical practice. The journal welcomes submission of high-quality original studies and review articles in a wide range of scientific fields, including anatomy, anesthesiology, animal welfare, behavior, epidemiology, genetics, heredity, infectious disease, molecular biology, oncology, pharmacology, pathogenic mechanisms, physiology, surgery, theriogenology, toxicology, and vaccinology. Species of interest include production animals, companion animals, equids, exotic animals, birds, reptiles, and wild and marine animals. Reports of laboratory animal studies and studies involving the use of animals as experimental models of human diseases are considered only when the study results are of demonstrable benefit to the species used in the research or to another species of veterinary interest. Other fields of interest or animals species are not necessarily excluded from consideration, but such reports must focus on novel research findings. Submitted papers must make an original and substantial contribution to the veterinary medicine knowledge base; preliminary studies are not appropriate.
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