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光敏剂替奥卟啉锡在犬和大鼠体内的比较药代动力学

Comparative pharmacokinetics of the photosensitizer tin-etiopurpurin in dogs and rats.

作者信息

Frazier D L, Barnhill M A, Vodinh T, Legendre A M, Overholt B F

机构信息

Department of Environmental Practice and Urban Practice, University of Tennessee College of Veterinary Medicine, Knoxville 37901.

出版信息

J Vet Pharmacol Ther. 1992 Sep;15(3):275-81. doi: 10.1111/j.1365-2885.1992.tb01017.x.

Abstract

Photodynamic therapy is a promising new treatment for local eradication of cancer. Little work has been done to define the pharmacokinetics of photodynamic drugs or the variability in drug disposition that may occur between different species and pathophysiological states of tissues. Pharmacokinetic studies of tin-etiopurpurin (SnET2), a lipophilic photosensitizer, were conducted on six Beagle dogs and six Sprague-Dawley rats. Blood was collected up to 24 h following drug administration for measurement of tin-etiopurpurin concentration. Dogs and rats were euthanatized 24 h post-administration and tissues were collected for drug analyses. The plasma drug concentrations were best described by a 2-compartment model (Ct = Ae-alpha t + Be-beta t). Median distribution and elimination half-lives were 0.24 and 0.34 h and 10.21 and 5.25 h for dogs and rats, respectively. The apparent volumes of distribution were 4.26 +/- 1.75 L/kg for dogs and 1.84 +/- 0.36 L/kg for rats. Systemic clearance was 7.56 +/- 2.45 ml/kg/min and 6.63 +/- 0.91 ml/kg/min for dogs and rats, respectively. Drug was detected in all tissues analyzed 24 h after drug administration. Drug was detected only sporadically in skin and muscle and was generally below the limit of detection of the assay. Where comparisons could be made, concentrations of SnET2 were significantly greater in all tissues except jejunum of rats compared to dogs 24 h after drug administration.

摘要

光动力疗法是一种用于局部根除癌症的很有前景的新疗法。目前,在确定光动力药物的药代动力学或不同物种及组织病理生理状态之间可能出现的药物处置变异性方面所做的工作很少。对一种亲脂性光敏剂锡-依替泊卟啉(SnET2)进行了药代动力学研究,研究对象为6只比格犬和6只斯普拉格-道利大鼠。给药后长达24小时采集血液,用于测定锡-依替泊卟啉浓度。给药24小时后对犬和大鼠实施安乐死,并采集组织进行药物分析。血浆药物浓度用二室模型(Ct = Ae-alpha t + Be-beta t)能得到最佳描述。犬和大鼠的中位分布半衰期和消除半衰期分别为0.24和0.34小时以及10.21和5.25小时。犬的表观分布容积为4.26±1.75升/千克,大鼠为1.84±0.36升/千克。犬和大鼠的全身清除率分别为7.56±2.45毫升/千克/分钟和6.63±0.91毫升/千克/分钟。给药24小时后,在所有分析的组织中均检测到药物。仅在皮肤和肌肉中偶尔检测到药物,且一般低于检测限。在可以进行比较的情况下,给药24小时后,除大鼠空肠外,所有组织中SnET2的浓度均显著高于犬。

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