Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; German Center for Infection Research (DZIF), Heidelberg Partner Site, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; German Center for Infection Research (DZIF), Heidelberg Partner Site, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
J Pharm Sci. 2020 Jun;109(6):2090-2094. doi: 10.1016/j.xphs.2020.03.012. Epub 2020 Mar 20.
Intestinal absorption of orally administered peptides is often negligible because one or more key requirements for successful absorption (water solubility, peptic resistance, mucosal permeation) are not met. Due to its high water solubility and stability in the gastro-intestinal tract, vancomycin is an ideal model peptide for evaluating the factors influencing the critical step of mucosal permeation. Therefore, to support formulation development for the systemic oral delivery of peptide therapeutics, we investigated the pharmacokinetics of vancomycin in beagle dogs after intravenous and oral administration comparing enteric encapsulated drug to the drug in solution, which revealed mean absolute bioavailabilities of 0.27% and 1.66%, respectively. Additionally, in depth pharmacokinetic analyses of intravenously administered vancomycin revealed a deep compartment slowly releasing the compound over many hours into the blood.
由于口服肽类药物的肠道吸收通常可以忽略不计，因为成功吸收（水溶性、耐胃酸、黏膜渗透）所需的一个或多个关键要求都无法满足。由于万古霉素具有高水溶性和在胃肠道中的稳定性，因此它是评估影响黏膜渗透关键步骤的各种因素的理想模型肽。因此，为了支持肽类治疗药物系统口服给药的制剂开发，我们在比格犬中研究了静脉和口服给予包肠溶衣的药物与溶液中药物后的万古霉素药代动力学，结果分别显示，绝对生物利用度分别为 0.27%和 1.66%。此外，对静脉给予的万古霉素进行的深入药代动力学分析表明，一个深层隔室在数小时内将药物缓慢释放到血液中。
