14C-Isomazole Disposition in Man After Oral Administration View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1991-11

AUTHORS

James R. Woodworth, Allyn F. DeLong, A.F. Fasola, Samuel Oldham

ABSTRACT

A 50-mg dose containing 50 microCi 14C-isomazole was administered orally to five healthy male volunteers. Blood, plasma, urine, feces, and saliva were collected and measured for total 14C; in addition, all collections except feces were measured for parent drug (ISO) and three metabolites: hydroxyisomazole (OHISO) and sulfone (SULF) and hydroxysulfone (OHSULF) analogues. Urine and fecal recoveries accounted for 97.0% of the drug administered, with 62.6% excreted in urine and 32.4% in feces. Only 47% of the drug recovered in urine could be identified, with ISO the largest constituent. Total plasma 14C peaked at 1.5 hr, indicating rapid absorption, and produced a mean half-life of 3.7 hr. This was similar to the total 14C half-life found in blood (3.1 hr) but longer than in red blood cells (1.8 hr) or saliva (1.4 hr), suggesting that different ISO-related compounds contributed to the results found in each fluid or tissue. An unidentified metabolite(s) composed a large portion of circulating plasma 14C and produced the longer half-life encountered in plasma. ISO exhibited a short half-life (1.35 hr), a high oral clearance (Cls/F; 24.2 ml/min/kg), and some extravascular distribution (V beta; 3.07 L/kg). Total 14C in red blood cells and saliva related very well to plasma ISO disposition, suggesting preferential distribution of parent drug across cellular membranes. The estimated RBC:plasma ISO ratio (1.79) confirmed this hypothesis. Saliva may be used as a noninvasive means to monitor ISO disposition. More... »

PAGES

1413-1417

Identifiers

URI

http://scigraph.springernature.com/pub.10.1023/a:1015857324838

DOI

http://dx.doi.org/10.1023/a:1015857324838

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1029218687

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/1798679


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