Filippich L J, Charles B G, Sutton R H, Bucher A M
The University of Queensland, Queensland, 4072.
Aust Vet J. 2004 Jun;82(6):366-9. doi: 10.1111/j.1751-0813.2004.tb11106.x.
To determine the pharmacokinetics of carboplatin in sulphur-crested cockatoos, so that its use in clinical studies in birds can be considered.
A pharmacokinetic study of carboplatin, following a single intravenous (IV) or intraosseus (IO) infusion over 3 min, was performed in six healthy sulphur-crested cockatoos (Cacatua galerita).
Birds were anaesthetised and a jugular vein cannulated for blood collection. Carboplatin (5 mg/kg) was infused over 3 min by the IV route in four birds via the contralateral jugular vein, and by the IO route in two birds via the ulna. Serial blood samples were collected for 96 h after initiation of the infusion. Tissue samples from 11 organs were obtained at necropsy, 96 h after carboplatin administration. Total Pt and filterable Pt in plasma and tissue Pt concentrations were assayed by inductively coupled plasma-mass spectrometry. A noncompartmental pharmacokinetic analysis was performed on the plasma data.
The mean +/- SD for the Cmax of filterable Pt was 27.3 +/- 4.06 mg/L and in all six birds occurred at the end of the 3 min infusion, thenceforth declining exponentially over the next 6 h to an average concentration of 0.128 +/- 0.065 mg/L. The terminal half-life (T1/2) was 1.0 +/- 0.17 h, the systemic clearance (CI) was 5.50 +/- 1.06 mL/min/kg and the volume of distribution (Vss) was 0.378 +/- 0.073 L/kg. The extrapolated area under the curve (AUC0-x) was 0.903 +/- 0.127 mg/mL x min; the area extrapolated past the last (6 h) data point to infinite time averaged only 1.25% of the total AUC0-x. The kidneys had the greatest accumulation of Pt (7.04 +/- 3.006 microg/g), followed by the liver (3.08 +/- 1.785 microg/g DM).
Carboplatin infusion in sulphur-crested cockatoos produced mild, transient alimentary tract signs and the Pt plasma concentration was similar whether carboplatin was given intravenously or intraosseously. Filterable plasma Pt concentrations for carboplatin persisted longer than for cisplatin, due mostly to the difference in systemic clearance between these drugs in sulphur-crested cockatoos. The distribution of tissue Pt after carboplatin administration was similar to that reported for cisplatin in sulphur-crested cockatoos. Despite anatomical, physiological and biochemical differences among animal species, the pharmacokinetic disposition of filterable Pt in the sulphur-crested cockatoo shares some features with the kinetics reported previously in other animals and human beings.
确定卡铂在硫冠凤头鹦鹉体内的药代动力学，以便考虑将其用于鸟类的临床研究。
对6只健康的硫冠凤头鹦鹉（白凤头鹦鹉）进行了一项卡铂的药代动力学研究，通过静脉内（IV）或骨内（IO）在3分钟内单次输注。
对鸟类进行麻醉，并通过颈静脉插管进行采血。4只鸟通过对侧颈静脉经静脉途径在3分钟内输注卡铂（5mg/kg），2只鸟通过尺骨经骨内途径输注。输注开始后96小时收集系列血样。在卡铂给药96小时后尸检时获取11个器官的组织样本。通过电感耦合等离子体质谱法测定血浆中的总铂和可滤过铂以及组织铂浓度。对血浆数据进行非房室药代动力学分析。
可滤过铂的Cmax的平均值±标准差为27.3±4.06mg/L，在所有6只鸟中均在3分钟输注结束时出现，此后在接下来的6小时内呈指数下降至平均浓度0.128±0.065mg/L。终末半衰期（T1/2）为1.0±0.17小时，全身清除率（CI）为5.50±1.06mL/分钟/千克，分布容积（Vss）为0.378±0.073L/千克。曲线下外推面积（AUC0-x）为0.903±0.127mg/mL·分钟；从最后一个（6小时）数据点外推至无限时间的面积平均仅占总AUC0-x的1.25%。肾脏中铂的蓄积量最大（7.04±3.006微克/克），其次是肝脏（3.08±1.785微克/克干物质）。
硫冠凤头鹦鹉输注卡铂产生轻度、短暂的消化道体征，无论卡铂是静脉内给药还是骨内给药，铂的血浆浓度相似。卡铂的可滤过血浆铂浓度持续时间比顺铂长，这主要是由于硫冠凤头鹦鹉体内这两种药物全身清除率的差异。卡铂给药后组织铂的分布与硫冠凤头鹦鹉中顺铂的报道相似。尽管动物物种之间存在解剖学、生理学和生化差异，但硫冠凤头鹦鹉中可滤过铂的药代动力学处置与先前在其他动物和人类中报道的动力学有一些共同特征。
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