ArticleZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences2023
Effects of plateau hypoxia on pharmacokinetic parameters and cerebral-blood distribution of levetiracetam in rats.
Article in Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesPlateau hypoxia exposure causes changes in pharmacokinetic parameters and cerebral-blood distribution of drugs, including many substrates of P-glycoprotein (P-gp). Levetiracetam, a kind of antiepileptic drugs, is a substrate of P-gp. Whether plateau hypoxia exposure changes its pharmacokinetic characteristics and cerebral-blood distribution remains unclear. This study aims to investigate the effects of plateau hypoxia on the pharmacokinetics and cerebra-blood distribution of levetiracetam.
methodsWistar rats were divided into a low-altitude control group, a high-altitude group, a solvent group, and a P-gp induction group. After 24 h of exposure at altitude of 4 010 m, rats in the high-altitude group were given levetiracetam orally or intravenously. The plasma was respectively collected at 0.083, 0.25, 0.5, 0.83, 1.25, 2, 4, 6, 8, 10, 12, and 24 h after oral administration of the drug, while both plasma and brain were respectively collected at 5, 45, 60,120 and 240 min after intravenous injection. After 3 days administration of dexamethasone, plasma and brain of rats in the P-gp induction group were collected at 120 min after intravenously giving levetiracetam. Plasma and brain concentrations of the drug were determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The expression of P-gp in blood-brain barrier was detected by Western blotting.
resultsCompared with the low-altitude control group, the area under the curve (AUC) and mean residence time (MRT) of levetiracetam were respectively decreased by 14.69% (
conclusionsAfter acute plateau hypoxia exposure, the pharmacokinetic of levetiracetam in rats are altered, and the cerebral-blood distribution of the drug in rats is decreased, which may be related to the up-regulation of P-gp expression on the blood-brain barrier.
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