Subject(s)
Breath Tests , Diarrhea/enzymology , Hydrogen/analysis , beta-Galactosidase/deficiency , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Chronic Disease , Female , Humans , Infant , Lactase , Lactose Intolerance/diagnosis , Lactose Intolerance/enzymology , Male , Middle AgedABSTRACT
1. Oral doses of [14C]salicylidene benzylamine were well absorbed by rats and dogs and excreted mainly in the urine (92% dose by rat in 24 h and 84% by dog in 48 h). 2. After 50, 100 and 300 mg/kg oral doses to rats, peak mean plasma 14C concn. (mainly salicylic acid) of 77, 243 and 396 micrograms equiv./ml respectively were reached between 2 and 4 h and maintained at this level until about 7.5 h. 14C was cleared more rapidly from the plasma of male rats than from that of female rats. After 44, 85 and 300 mg/kg oral doses to dogs, peak mean plasma 14C concn. (mainly salicylic acid) of 114, 194 and 320 micrograms equiv./ml respectively were reached at 4 h and then declined with a half-life of 6-7 h. 3. Tissue 14C concn. in both species were greatest at the times of peak plasma 14C concn., but in general were lower than those in the corresponding plasma. 4. The major components in rat and dog urine were salicyl alcohol, salicylic acid and salicyluric acid, the first two being excreted partly as glucuronic acid/sulphate conjugates. After initial hydrolysis of salicylidene benzylamine to salicylaldehyde, approximately equal amounts were reduced and oxidized to the corresponding alcohol and acid respectively.
Subject(s)
Anti-Inflammatory Agents/metabolism , Schiff Bases/metabolism , Animals , Dogs , Female , Male , Rats , Rats, Inbred Strains , Salicylates/metabolism , Sex Factors , Species Specificity , Tissue DistributionABSTRACT
GLC methods were developed for the investigation of impurities in bakrine and saddamine. The method used for bakrine was unsuitable for saddamine since two possible saddamine impurities, benzylamine and salicylaldehyde, reacted very readily in solution to form saddamine, thus giving a false low value for the original concentration of these impurities. The method devised for saddamine involved silylation, which greatly reduced the possibility of saddamine formation from its precursors and also enabled the detection of another possible impurity, salicylic acid. The method described has an obvious application to the determination of other Schiff bases.
Subject(s)
Amines/analysis , Benzylamines/analysis , Schiff Bases/analysis , Anti-Inflammatory Agents/analysis , Chromatography, Gas , Drug Contamination , MethodsABSTRACT
The metabolism of 14C-saddamine radiolabelled in the benzylamine moiety has been investigated in man after oral administration. 14C-Hippuric acid was found to be the only radiolabelled urinary metabolite, the overall amount of which was equivalent to over 95% of the dose. The time taken for elimination of 50% of the dose in the urine was approximately five hours and the corresponding value for 14C-benzylamine hydrochloride was less than one hour.
Subject(s)
Amines/metabolism , Anti-Inflammatory Agents/metabolism , Benzylamines/metabolism , Schiff Bases/metabolism , Biotransformation , Hippurates/metabolism , Humans , Time FactorsABSTRACT
The fate of 14C-benzylamine after oral administration as the hydrochloride has been investigated in two male volunteers. Over 98% of the administered radiolabel was excreted in the urine as 14C-hippuric acid within 24 hours. The rate of urinary hippuric acid excretion was extremely rapid, with more than 90% of the dose excreted after three hours.
