The fate of ultra-low viscosity 14C-hydroxypropyl methylcellulose in rats following gavage administration.

Abstract

The disposition of 14C-Hydroxypropyl methylcellulose (HPMC) with a viscosity of 2.25 centipoise was studied in male and female Sprague-Dawley rats following a single 500 mg/kg body weight gavage dose, or five consecutive daily doses. Recoveries for the single dose were: feces, greater than 99%; urine, approximately 1%; carcass and tissues, approximately 0.2%; expired air, 0.07%; and bile, 0.05%. Plasma radioactivity had a monophasic excretion half-life of approximately 2 hours for either sex. The majority of the residual radioactivity in the tissues was found in the gastrointestinal tract. The absorbed radioactivity in the urine, based on thin layer chromatography (TLC) analyses, represented methyl ethers of glucose and oligomers; this amounted to 0.56% recovered in a study in which urine samples were isolated from possible contamination by radioactivity in the feces. The 0.56% correlated well with the 0.53% portion of the original dosing solution which consisted of cellulose units with an average molecular weight of less than 1000. Recovery of radioactivity in the feces of rats on the 5-day dosing regimen was 97% and 102% for males and females, respectively, without any evidence for accumulation in tissues. Approximately 1% was recovered in the urine. Thus, the results of this work show that ultra-low viscosity 2.25 centipoise HPMC was only minimally absorbed with essentially all of a single 500 mg/kg gavage dose, or 5 daily consecutive doses, being excreted unabsorbed in the feces.