title: 14C-isomazole disposition in man after oral administration.
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.
authors.affiliation: Lilly Laboratory for Clinical Research, Wishard Memorial Hospital, Indianapolis, Indiana 46202.
authors.forename: J R
authors.initials: JR
authors.lastname: Woodworth
authors.forename: A F
authors.initials: AF
authors.lastname: DeLong
authors.forename: A F
authors.initials: AF
authors.lastname: Fasola
authors.forename: S
authors.initials: S
authors.lastname: Oldham
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002250:Carbon Radioisotopes; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005243:Feces / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D012463:Saliva / Q000737:chemistry
chemical_list: D002250:Carbon Radioisotopes; D002316:Cardiotonic Agents; D007093:Imidazoles; C029758:sulmazole