Pharmacokinetics of gamma-hydroxybutyric acid in 6-week-old swine (Sus scrofa domesticus) after intravenous and oral administration

IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY
Charlotte Cuypers, Mathias Devreese, Katleen Van Uytfanghe, Christophe Stove, Stijn Schauvliege
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Abstract

Sedative as well as protective effects during hypoxia have been described for gamma-hydroxybutyric acid (GHB). Six swine (Sus scrofa domesticus) of 6 weeks old were administered NaGHB at a dose of 500 mg/kg intravenously (IV) and 500 and 750 mg/kg orally (PO) in a triple cross-over design. Repeated blood sampling was performed to allow pharmacokinetic analysis of GHB. Whole blood concentration at time point 0 after IV administration was 1727.21 ± 280.73 μg/mL, with a volume of distribution of 339.45 ± 51.41 mL/kg and clearance of 164.94 ± 47.05 mL/(kg h). The mean peak plasma concentrations after PO administration were 326.57 ± 36.70 and 488.01 ± 154.62 μg/mL for 500 mg/kg and 750 mg/kg, respectively. These were recorded at 1.42 ± 0.72 and 1.58 ± 0.58 h after PO dose for GHB 500 mg/kg and 750 mg/kg, respectively. The elimination half-life for IV and PO 500 mg/kg and PO 750 mg/kg dose was respectively 1.33 ± 0.30, 1.16 ± 0.31 and 1.11 ± 0.33 h. The bioavailability (F) for PO administration was 45%. No clinical adverse effects were observed after PO administration. Deep sleep was seen in one animal after IV administration, other animals showed head pressing and ataxia.

-羟基丁酸在6周龄猪(苏斯scrofa domesticus)体内静脉和口服给药的药代动力学。
-羟基丁酸(GHB)在缺氧时具有镇静和保护作用。6头6周龄的猪(苏斯scrofa domesticus)采用三交叉试验设计,以500 mg/kg的静脉注射剂量(IV)和500、750 mg/kg的口服剂量(PO)给药。反复抽血进行GHB药代动力学分析。静脉给药后0时间点全血浓度为1727.21±280.73 μg/mL,体积分布为339.45±51.41 mL/kg,清除率为164.94±47.05 mL/(kg h)。500 mg/kg和750 mg/kg组PO给药后平均血药峰浓度分别为326.57±36.70和488.01±154.62 μg/mL。分别在PO给药后1.42±0.72和1.58±0.58 h记录了GHB 500 mg/kg和750 mg/kg。IV、PO 500 mg/kg和PO 750 mg/kg剂量的消除半衰期分别为1.33±0.30、1.16±0.31和1.11±0.33 h。PO给药的生物利用度F为45%。给药后无临床不良反应。静脉给药后1只动物出现深度睡眠,其余动物出现头部压迫和共济失调。
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来源期刊
CiteScore
3.10
自引率
15.40%
发文量
69
审稿时长
8-16 weeks
期刊介绍: The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.
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