Chemical reactivity and intracavitary application of alkylating sugar alcohol derivatives

• Published in: Oncology Vol. 37 Suppl 1; p. 109
• Main Authors: Kerpel-Fronius, S, Csetényi, J, Hegedüs, L, Horváth, I P, Ringwald, G, Töttössy, B, Eckhardt, S
• Format: Journal Article
• Language: English
• Published: Switzerland 1980
• Subjects: Drug Stability; Erythritol - administration & dosage; Erythritol - analogs & derivatives; Erythritol - metabolism; Half-Life; Humans; Injections, Intraperitoneal; Plasma - metabolism
• ISSN: 0030-2414
• DOI: 10.1159/000225507

Lycurium [1,4-di-(methylsulfonyloxy-ethylamino)-1,4-didesoxy-erythrioldimethylsulfonate; R-74; NSC-122402] undergoes rapid hydrolysis in aqueous solutions. The concentration of the alkylating compound(s), demonstrated by the 4-(4'-nitrobenzyl)pyridine reaction, decreases approximately by 80% in 10 min following the dissolution of the drug in saline. In patients peak plasma concentration of radioactivity after the intracavitary injection of 14C-labelled Lycurim is observed between 4 and 6 h. It is assumed, therefore, that only a negligible amount of pharmacologically active alkylating compounds reaches the circulation after intracavitary application. This conclusion is supported by clinical experience showing that intracavitary administration of the same amount of Lycurim causes much milder systemic side-effects than intravenous injection. A dose escalation study was started to determine the applicability of Lycurim in the form of high volume intraperitoneal instillation ('belly bath') for the treatment of ovarian cancer.