对乙酰氨基酚静脉给药时间对家兔药代动力学及眼部处置的影响
Influence of the Time of Intravenous Administration of Paracetamol on its Pharmacokinetics and Ocular Disposition in Rabbits.
作者信息
Karbownik Agnieszka, Bienert Agnieszka, Płotek Włodzimierz, Grabowski Tomasz, Cerbin-Koczorowska Magdalena, Wolc Anna, Grześkowiak Edmund
机构信息
Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, ul. Św. Marii Magdaleny 14, 61-861, Poznań, Poland.
Department of Teaching Anaesthesiology and Intensive Therapy, Poznan University of Medical Sciences, ul. Św. Marii Magdaleny 14, 61-861, Poznań, Poland.
出版信息
Eur J Drug Metab Pharmacokinet. 2017 Jun;42(3):489-498. doi: 10.1007/s13318-016-0365-y.
BACKGROUND AND OBJECTIVES
Paracetamol is one of the most common analgesics and antipyretics applied in health care. The aim of the study was to investigate the influence of the time-of-day administration on the paracetamol pharmacokinetics and its penetration into aqueous humour (AH).
METHODS
Rabbits were divided into three groups: I-receiving paracetamol at 08.00 h, II-receiving paracetamol at 16.00 h, and III-receiving paracetamol at 24.00 h. Paracetamol was administered intravenously at a single dose of 35 mg/kg. The concentrations of paracetamol and its metabolite (paracetamol glucuronide) in the plasma, as well as in AH were measured with the validated HPLC-UV method.
RESULTS
No significant differences in the pharmacokinetic parameters of paracetamol was observed. When the drug was administered at 24.00 h, elimination half-life (t ) of paracetamol glucuronide was longer than when the drug was administered 08.00 h (P = 0.0193). In addition, a statistically significant increase in the paracetamol glucuronide/paracetamol ratio was observed when the drug was administered at 08.00 vs. 16.00 h (P ≤ 0.0001) and 24.00 h (P ≤ 0.0001).
CONCLUSIONS
There was no chronobiological effect on the pharmacokinetic parameters of paracetamol.
背景与目的
对乙酰氨基酚是医疗保健中最常用的止痛和退烧药之一。本研究的目的是调查给药时间对乙酰氨基酚药代动力学及其进入房水（AH）的影响。
方法
将兔子分为三组：第一组在08:00接受对乙酰氨基酚，第二组在16:00接受对乙酰氨基酚，第三组在24:00接受对乙酰氨基酚。以35mg/kg的单剂量静脉注射对乙酰氨基酚。采用经过验证的高效液相色谱-紫外法测定血浆和房水中对乙酰氨基酚及其代谢物（对乙酰氨基酚葡萄糖醛酸苷）的浓度。
结果
未观察到对乙酰氨基酚药代动力学参数有显著差异。当在24:00给药时，对乙酰氨基酚葡萄糖醛酸苷的消除半衰期（t）比对乙酰氨基酚在08:00给药时更长（P = 0.0193）。此外，当在08:00与16:00给药时（P≤0.0001）以及在08:00与24:00给药时（P≤0.0001），观察到对乙酰氨基酚葡萄糖醛酸苷/对乙酰氨基酚比值有统计学显著增加。
结论
对乙酰氨基酚的药代动力学参数不存在时间生物学效应。
Zotero 插件