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|標題:||Microdialysis combined blood sampling technique for the determination of rosiglitazone and glucose in brain and blood of gerbils subjected to cerebral ischemia||作者:||Sheu, W.H.H.
|Project:||Journal of Pharmaceutical and Biomedical Analysis||期刊/報告no：:||Journal of Pharmaceutical and Biomedical Analysis, Volume 54, Issue 4, Page(s) 759-764.||摘要:||
Rosiglitazone is a potent synthetic peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist which improves glucose control in the plasma and reduces ischemic brain injury. However, the pharmacokinetics of rosiglitazone in the brain is still unclear. In this study, a method using liquid chromatography-mass spectrometry coupled with microdialysis and an auto-blood sampling system was developed to determine rosiglitazone and glucose concentration in the brain and blood of gerbils subjected to treatment with rosiglitazone (3.0 mg kg(-1), i.p.). The results showed the limit of detection was 0.04 mu g L(-1) and the correlation coefficient was 0.9997 for the determination of rosiglitazone in the brain. The mean parameters, maximum drug concentration (C(max)) and the area under the concentration-time curve from time zero to time infinity (AUC(inf)), following rosiglitazone administration were 1.06 +/- 0.28 mu g L(-1) and 296.82 +/- 44.67 mu g min L(-1), respectively. The time to peak concentration (C(max) or T(max)) of rosiglitazone occurred at 105 +/- 17.10 min, and the mean elimination half-life (t(1/2)) from brain was 190.81 +/- 85.18 min after administration of rosiglitazone. The brain glucose levels decreased to 71% of the basal levels in the rosiglitazone-treated group when compared with those in the control (p < 0.01). Treatment with rosiglitazone decreased blood glucose levels to 80% at 1 h after pretreatment of rosiglitazone (p < 0.05). In addition, pretreatment with rosiglitazone significantly reduced the cerebral infarct volume compared with that of the control group. These findings suggest that this method may be useful for simultaneous and continuous determination of rosiglitazone and glucose concentrations in brain and plasma. Rosiglitazone was effective at penetrating the blood-brain barrier as evidenced by the rapid appearance of rosiglitazone in the brain, and rosiglitazone may contribute to a reduction in the extent of injuries related to cerebral ischemic stroke via its hypoglycemic effect. (C) 2010 Elsevier B.V. All rights reserved.
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