Distribution of trimethoprim-sulfamethoxazole in tissues of rhesus monkeys.
Distribution of trimethoprim-sulfamethoxazole in tissues of rhesus monkeys.
复制标题
甲氧苄啶-磺胺甲恶唑在恒河猴组织中的分布。
DOI：
--
复制
发表时间：
1973
影响因子：
6.4
通讯作者：
C. Kunin
中科院分区：
文献类型：
--
作者：
W. Craig;C. Kunin
在建立与人相当的血清水平后，研究了甲氧苄啶（TMP）和非乙酰化磺胺甲恶唑（SMZ）在平衡状态下恒河猴组织中的分布。非乙酰化SMZ在组织中的浓度始终低于血清中的浓度，肾脏、肺和心脏的浓度最高。相比之下，除脑、皮肤和脂肪外，组织中TMP浓度高于血清。肾脏和肝脏对TMP的吸收最大。组织中SMZ与TMP的比例显著低于血清中，低于抗菌协同作用的最佳比例20:1。两种药物从组织中消失的速度与从血清中消除的速度相同。甲氧苄啶（TMP）和磺胺甲恶唑（SMZ）在动物和人体内的药代动力学已有报道[1-3]。分布计算表明，组织对TMP的吸收显著，而对SMZ的吸收不显著。来自患者的活检材料以及对大鼠、小鼠和兔子组织的分布研究表明，组织中TMP的浓度超过血清，而组织中SMZ的水平低于血清[3-5]。我们设计了以下研究，以确定这些药物在灵长类动物组织中的分布，其血清水平与人类相当。
The distributions of trimethoprim (TMP) and nonacetylated sulfamethoxazole (SMZ) were studied in tissues of rhesus monkeys at equilibrium after establishment of serum levels comparable to those in man. Concentrations of nonacetylated SMZ in tissue were always lower than those in serum, with the highest concentrations in kidney, lung, and heart. In contrast, concentrations of TMP in tissue were greater than those in serum, except in brain, skin, and fat. The greatest uptake of TMP by tissues was observed in kidney and liver. The ratio of SMZ to TMP was significantly less in tissue than in serum and was lower than the optimal 20:1 ratio for antibacterial synergy. The rate of disappearance of both drugs from tissues was identical to their rate of elimination from serum. The pharmacokinetics of trimethoprim (TMP) and sulfamethoxazole (SMZ) in animals and man have been previously reported [1-3]. Calculations of distribution have suggested significant uptake of TMP but not of SMZ by tissues. Biopsy material from patients and distribution studies in tissues of the rat, mouse, and rabbit have shown that the concentration of TMP in tissues exceeds that in serum, whereas levels of SMZ are lower in tissues than in serum [3-5]. We designed the following investigations to determine the distribution of these drugs in the tissues of primates at equilibrium with serum levels comparable to those in man.