Properties, stability, assay, and preliminary pharmacokinetics of the immunomodulatory 1,2-O-isopropylidene-3-O-3'(N',N'-dimethylamino-n-propyl)-D-glucofuranose hydrochloride.
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.
D000276:Adjuvants, Immunologic / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D002626:Chemistry, Pharmaceutical; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D004285:Dogs; D004355:Drug Stability; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D007700:Kinetics; D011199:Potentiometry; D012266:Ribose / Q000031:analogs & derivatives; D012995:Solubility
D000276:Adjuvants, Immunologic; D012266:Ribose; D005944:Glucosamine; C018424:amiprilose