Tan J S, Salstrom S J, File T M
Am J Med. 1984 Oct 19;77(4C):33-6.
A skin window technique was used to investigate the ability of three of the newer cephalosporins, moxalactam, cefoperazone, and ceftriaxone, to enter the interstitial fluid of normal, healthy volunteers. Intravenous and intramuscular routes of delivery were compared. The method of delivery did not greatly affect diffusibility with moxalactam and ceftriaxone. Intravenous infusion resulted in greater diffusibility with cefoperazone than did intramuscular injection. Cefoperazone demonstrated the lowest diffusibility of the three test drugs. Ceftriaxone, administered at one-half the dose of cefoperazone and moxalactam, demonstrated the greatest ability to diffuse into interstitial fluid despite its high level of binding to plasma protein. The better diffusibility of ceftriaxone may be explained by a persistently high concentration gradient provided by its long serum half-life. Overall, the results support the concept of the concentration gradient as an important determinant of antibiotic activity.
采用皮肤窗技术研究了三种新型头孢菌素（拉氧头孢、头孢哌酮和头孢曲松）进入正常健康志愿者间质液的能力。比较了静脉和肌肉注射两种给药途径。给药方式对拉氧头孢和头孢曲松的扩散性影响不大。静脉输注头孢哌酮比肌肉注射具有更高的扩散性。在三种受试药物中，头孢哌酮的扩散性最低。尽管头孢曲松与血浆蛋白的结合水平较高，但以头孢哌酮和拉氧头孢一半的剂量给药时，其扩散到间质液中的能力最强。头孢曲松更好的扩散性可能是由于其较长的血清半衰期提供了持续较高的浓度梯度。总体而言，这些结果支持浓度梯度是抗生素活性重要决定因素的概念。
