Pharmacokinetics of fentanyl citrate and norfentanyl in Holstein calves and effect of analytical performances on fentanyl parameter estimation
Pharmacokinetics of fentanyl citrate and norfentanyl in Holstein calves and effect of analytical performances on fentanyl parameter estimation
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DOI：
10.1111/jvp.12501
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发表时间：
2018-08-01
影响因子：
1.3
通讯作者：
Mochel, J. P.
中科院分区：
文献类型：
--
作者：
Smith, J. S.;Coetzee, J. F.;Mochel, J. P.
本研究描述了静脉内给药（i. v.）枸橼酸芬太尼及其主要代谢产物去甲芬太尼。8头3- 4周龄小牛（58.6 +/- 2.2kg）以5.0g/kg的单剂量静脉注射给予枸橼酸芬太尼。从0至24小时收集血样。使用液相色谱-质谱法测定血浆（或）芬太尼浓度，定量下限（LLOQ）为0.03 ng/ml。为了探索分析性能对芬太尼参数估计的影响，然后使用假设的LLOQ值0.05 ng/ml重复非房室药代动力学分析。芬太尼和去甲芬太尼的终末消除半衰期估计分别为12.7和3.6小时。芬太尼的全身清除率估计为2.0Lhr（-1）kg（-1），稳态分布容积为24.8L/kg，提取率为0.42。在假设的LLOQ为0.05 ng/ml芬太尼半衰期时，稳态分布容积和清除率分别为3.0 hr、8.8 L/kg和3.4 L kg（-1）hr（-1）。枸橼酸芬太尼以5.0 g/kg静脉注射给药可达到与其他物种镇痛相关的水平。药代动力学参数应根据LLOQ进行解释，因为下限可影响估计的参数，如消除半衰期或全身清除率，并对临床实践中的给药方案选择有显著影响。
This study describes the pharmacokinetics of intravenously administered (i.v.) fentanyl citrate, and its primary metabolite norfentanyl in Holstein calves. Eight calves (58.6 +/- 2.2kg), aged 3-4weeks, were administered fentanyl citrate at a single dose of 5.0g/kg i.v. Blood samples were collected from 0 to 24hr. Plasma (nor)fentanyl concentrations were determined using liquid chromatography with mass spectrometry and a lower limit of quantification (LLOQ) of 0.03ng/ml. To explore the effect of analytical performance on fentanyl parameter estimation, the noncompartmental pharmacokinetic analysis was then repeated with a hypothetical LLOQ value of 0.05ng/ml. Terminal elimination half-life was estimated at 12.7 and 3.6hr for fentanyl and norfentanyl, respectively. For fentanyl, systemic clearance was estimated at 2.0Lhr(-1)kg(-1), volume of distribution at steady-state was 24.8L/kg and extraction ratio was 0.42. At a hypothetical LLOQ of 0.05ng/ml fentanyl half-life, volume of distribution at steady-state and clearance were, respectively, of 3.0hr, 8.8L/kg and 3.4Lkg(-1)hr(-1). Fentanyl citrate administered i.v. at 5.0g/kg can reach levels associated with analgesia in other species. Pharmacokinetic parameters should be interpreted with respect to LLOQ, as lower limits can influence estimated parameters, such as elimination half-life or systemic clearance and have significant impact on dosage regimen selection in clinical practice.