关键词: UPLC-MS/MS bioavailability broiler bromhexine hydrochloride pharmacokinetics

Mesh : Animals Chickens Male Administration, Oral Female Bromhexine / pharmacokinetics administration & dosage Injections, Intravenous / veterinary Tandem Mass Spectrometry / veterinary Random Allocation Biological Availability Administration, Intravenous / veterinary

来  源:   DOI:10.1016/j.psj.2024.103838   PDF(Pubmed)

Abstract:
The current study aimed to investigate the pharmacokinetics of bromhexine hydrochloride in broilers after single intravenous (IV) and oral (PO) administration at 2.5 mg/kg body weight (BW). The trial adopted a randomized, parallel-controlled design, where 20 twelve-wk-old broilers were randomly assigned to either the PO or IV group. Blood samples were collected at predetermined time points, and plasma was further separated for analysis. The bromhexine hydrochloride concentrations in plasma samples were determined using an ultra-performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method. Noncompartmental analysis (NCA) using Phoenix software was conducted to analyze the concentration versus time data of bromhexine hydrochloride in every chicken. Subsequently, the main pharmacokinetic parameters between the 2 groups were statistically analyzed using SPSS software. Results from NCA revealed that after oral administration at 2.5 mg/kg BW, bromhexine hydrochloride exhibited slow absorption, reaching an average peak concentration of 32.72 ng/mL at 1.78 h. However, incomplete absorption was observed, with an absolute bioavailability of only 20.06% ± 10.84%. Additionally, bromhexine hydrochloride displayed wide distribution, with a steady-state distribution volume (VSS) of 22.55 ± 13.45 L/kg, and slow elimination, with a clearance (Cl) of 1.52 ± 0.38 L/h/kg. Furthermore, gender effects were assessed on the pharmacokinetics of bromhexine hydrochloride in broilers, revealing better absorption in male broilers compared to females. This disparity may be attributed to the faster blood flow and richer blood volume typically found in male broilers.
摘要:
本研究旨在研究以2.5mg/kg体重(BW)单次静脉(IV)和口服(PO)给药后盐酸溴己新在肉鸡中的药代动力学。该试验采用了随机,并行控制设计,其中20只12周龄的肉鸡被随机分配到PO或IV组。在预定的时间点采集血样,进一步分离血浆进行分析。使用超高效液相色谱-串联四极杆质谱(UPLC-MS/MS)方法测定血浆样品中盐酸溴己新的浓度。使用Phoenix软件进行非隔室分析(NCA)以分析每只鸡中盐酸溴己新的浓度与时间数据。随后,采用SPSS软件对两组间的主要药动学参数进行统计学分析。NCA的结果显示,口服2.5mg/kg体重后,盐酸溴己新表现出缓慢的吸收,在1.78h时达到32.72ng/mL的平均峰浓度。观察到不完全吸收,绝对生物利用度仅为20.06%±10.84%。此外,盐酸溴己新分布广泛,稳态分布体积(VSS)为22.55±13.45L/kg,缓慢消除,清除率(Cl)为1.52±0.38L/h/kg。此外,性别效应对盐酸溴己新在肉鸡体内的药代动力学进行了评估,与雌性相比,雄性肉鸡的吸收更好。这种差异可能归因于通常在雄性肉鸡中发现的更快的血流和更丰富的血液体积。
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