Generation of drug metabolite antigenicity in the intestinal mucosa

Both nitroreductase and transglutaminase activities have been assayed in the 10 000 x g supernatant fluids of rat intestine homogenates after Triton X-100 treatment. Incubation of 14C-nitrofurantoin in the intestine extract yielded protein-bound 14C-labeled products. Injection into rabbits of the conjugated protein similarly prepared with unlabeled nitrofurantoin elicited formation of antibodies against nitrofurantoin. These results suggest that intestinal metabolism and conjugation to protein of orally administered drugs may serve as a probable mechanism of drug allergy, and this may be accomplished by enzymatic coupling of relatively stable drug metabolites to protein carriers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26077/1/0000153.pd

Improved Nitromethane-Hyamine Method for the Chemical Determination of Nitrofurantoin in Whole Blood

Abstract The nitromethane-Hyamine method for assay of nitrofurantoin in whole blood has been improved: smaller volumes of blood (0.8 ml) are required, the sensitivity is greater (0.2 pg/mI), and the solution to be read is more stable than in the original method. The analysis detects 70 to 72% of 1 to 4 Ag of nitrofurantoin added per milliliter of whole blood. Blood concen-trations after the usual therapeutic peroral dose (100 mg) of nitrofurantoin are reported.</jats:p

THE DIFFERENTIAL DETERMINATION OF CONJUGATED HYDROXYSKATOLES IN HUMAN URINE

A method is described for the separation and estimation of 4-, 5-, 6-, and 7-hydroxyskatole sulfate esters in urine. After extraction from urine, the 5-, 6-, and 7-hydroxyskatole sulfate esters were hydrolyzed by a sulfatase preparation to the corresponding hydroxyskatoles. The 4-isomer was resistant to this enzymic hydrolysis. The hydroxyskatoles were then extracted by ethyl acetate from the hydrolyzate followed by extraction of the 4-sulfate ester by n-butanol. Each fraction was chromatographed on silica gel G thin layers, sprayed with a modified Ehrlich's reagent (p-N,N-bis(2-chloroethyl)aminobenzaldehyde), and the appropriate zones eluted from the chromatogram. The concentrations of each isomer originally present in the urine were estimated from the absorbances of the four eluates at their absorption maxima (ca. 600 mμ). The levels of the four isomeric skatolyl sulfates found in urines from 10 normal controls are given.</jats:p

THE STABILITY OF ADRENOCHROME AND ITS SOLUTIONS

The stability of adrenochrome solutions in the presence of several inorganic compounds has been studied.The purity and stability of several "aged" and commercial samples of adrenochrome have been evaluated.The stability of solutions of adrenochrome in some of the lower aliphatic alcohols has been examined.</jats:p

THE STABILITY OF ADRENOCHROME AND ITS SOLUTIONS

The stability of adrenochrome solutions in the presence of several inorganic compounds has been studied.The purity and stability of several "aged" and commercial samples of adrenochrome have been evaluated.The stability of solutions of adrenochrome in some of the lower aliphatic alcohols has been examined.</jats:p