Properties, stability, assay, and preliminary pharmacokinetics of the immunomodulatory 1,2-O-isopropylidene-3-O-3'(N',N'-dimethylamino-n-propyl)-D-glucofuranose hydrochloride. 1982

E R Garrett, and A Van Peer, and H Mahrous, and W Schuermann

1,2-O-Isopropylidene-3-O-3'(N',N'-dimethylamino-n-propyl)-D -glucofuranose hydrochloride (I) is a new agent with claimed immunomodulatory action and antiviral activity. Thin-layer chromatographic procedures and identifying tests were developed to separate the drug, its synthetic precursors, and solvolytic products, and were applied to stability studies. It is stable in 0.1 N NaOH at 60 degrees where its acid solvolysis product, 3-O-3'-(N',N'-dimethylamino-n-propyl)-D-glucose is readily degraded. The partition coefficient of I (pK'a = 9.28) between chloroform and plasma was 6.4 +/- 0.2 SEM between pH 10.5 and 11.0. Plasma and urine (0.5 ml) adjusted to pH 11.0 were extracted with 10 ml of chloroform and the extract evaporated. The reconstituted residue in 50 microliters of benzene, with the disopropylaminoethyl analog of I as an internal standard, was derivatized with 50 microliters of heptafluorobutyric anhydride at 60 degrees for 45 min and was evaporated and reconstituted in 100 microliters of benzene to be assayed for I by GLC with electron capture detection with a sensitivity of 5 ng/0.5 ml of biological fluid. The procedure was applied to pharmacokinetics in the dog and a two-compartment body model was observed with a terminal half-life of 103-130 min. At the 40-mg dose, 60-64% was excreted renally unchanged and 20-34% as unidentified metabolites. At the 200-mg dose 82-85% was excreted unchanged and 15-17% as unidentified metabolites. The respective renal clearances of I were 135 and 163 ml/min. The respective total clearances of I were 204 and 191 ml/min. These metabolites were apparently unextracted with chloroform from biological fluids at pH 11 and the liquid scintillation counting (LSC) assay of extracted radiolabeled I appeared synonomous with the GLC assay of I in such fluids.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D011199 Potentiometry Solution titration in which the end point is read from the electrode-potential variations with the concentrations of potential determining ions. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
D002626 Chemistry, Pharmaceutical Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use. Medicinal Chemistry,Chemistry, Pharmaceutic,Pharmaceutic Chemistry,Pharmaceutical Chemistry,Chemistry, Medicinal
D002849 Chromatography, Gas Fractionation of a vaporized sample as a consequence of partition between a mobile gaseous phase and a stationary phase held in a column. Two types are gas-solid chromatography, where the fixed phase is a solid, and gas-liquid, in which the stationary phase is a nonvolatile liquid supported on an inert solid matrix. Chromatography, Gas-Liquid,Gas Chromatography,Chromatographies, Gas,Chromatographies, Gas-Liquid,Chromatography, Gas Liquid,Gas Chromatographies,Gas-Liquid Chromatographies,Gas-Liquid Chromatography
D002855 Chromatography, Thin Layer Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Chromatography, Thin-Layer,Thin Layer Chromatography,Chromatographies, Thin Layer,Chromatographies, Thin-Layer,Thin Layer Chromatographies,Thin-Layer Chromatographies,Thin-Layer Chromatography
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D005944 Glucosamine 2-Amino-2-Deoxyglucose,Dona,Dona S,Glucosamine Sulfate,Hespercorbin,Xicil,2 Amino 2 Deoxyglucose,Sulfate, Glucosamine
D000276 Adjuvants, Immunologic Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Immunoactivators,Immunoadjuvant,Immunoadjuvants,Immunologic Adjuvant,Immunopotentiator,Immunopotentiators,Immunostimulant,Immunostimulants,Adjuvant, Immunologic,Adjuvants, Immunological,Immunologic Adjuvants,Immunological Adjuvant,Adjuvant, Immunological,Immunological Adjuvants
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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