Chemistry and clinical relevance of carbohydrate degradation in drugs. Issue 10 (October 2016)

• Record Type: Journal Article
• Authors: Pischetsrieder, Monika; Gensberger-Reigl, Sabrina; Atzenbeck, Lisa; Weigel, Ingrid
• Is Part Of: Drug discovery today. Volume 21:Issue 10(2016)
• Page Start: 1620
• Page End: 1631
• Publication Date: 2016-10
• Subjects: Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2016.06.011
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: Carbohydrate degradation products can be formed by heat sterilization of drugs. They are clinically relevant, e.g. in peritoneal dialysis- (PD) and infusion fluids. Clinical effects are caused by their cytotoxicity and activity to modify proteins. In PD, (p)GDPs may impair residual kidney function and damage the peritoneum. Studies on the chemistry of (p)GDP formation help to develop mitigation strategies. Abstract : Carbohydrate degradation products are formed during heat sterilization in drugs containing (poly-)glucose as osmotic agents. Given this situation, peritoneal dialysis fluids (PDFs) and infusion fluids are of particular clinical relevance, because these drugs deliver process contaminants either over a longer period or directly into the circulation of patients who are critically ill. For the development of suitable mitigation strategies, it is important to understand the reaction mechanisms of carbohydrate degradation during sterilization and how the resulting products interact with physiological targets at the molecular level. Furthermore, reliable, comprehensive, and highly sensitive quantification methods are required for product control and toxicological evaluation. Teaser: Purer drugs: carbohydrate degradation products are formed during heat sterilization of drugs containing (poly-)glucose as the osmotic agent, which can interact with cellular targets and lead to clinical complications.