Eppstein D A, Longenecker J P
Department of Biochemistry, Syntex Research, Palo Alto, California.
Crit Rev Ther Drug Carrier Syst. 1988;5(2):99-139.
The emergence of recombinant DNA technology has resulted in the large-scale production of a myriad of genetically engineered proteins and peptides, making many of them available for the first time for potential use as therapeutic entities. In addition, increased knowledge in the area of peptide/polypeptide hormones has resulted in an expansion of research efforts utilizing peptide synthetic chemistry, aimed toward developing novel therapeutic peptide drugs. Proteins and peptides cannot readily be administered by the conventional oral route, and thus alternative delivery methods to circumvent the necessity of frequent injections are being explored. This article reviews the current state-of-the-art technology of such methodologies, encompassing localized administration, administration to various body cavities (i.e., nasal, rectal, etc.), as well as controlled-release injectable or implantable systems. These different approaches result in quite different pharmacokinetics that may in part dictate which approach is best suited for a particular protein or peptide.
重组DNA技术的出现使得大量基因工程蛋白质和肽得以大规模生产,其中许多首次可作为潜在治疗实体使用。此外,肽/多肽激素领域知识的增加促使利用肽合成化学的研究工作不断扩展,旨在开发新型治疗性肽药物。蛋白质和肽难以通过传统口服途径给药,因此正在探索替代给药方法以避免频繁注射的必要性。本文综述了此类方法的当前先进技术,包括局部给药、向各种体腔(即鼻腔、直肠等)给药,以及控释注射或植入系统。这些不同的方法会产生截然不同的药代动力学,这可能在一定程度上决定哪种方法最适合特定的蛋白质或肽。