The Fate of Ultra-Low Viscosity¹⁴C-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.

A Single Subcutaneous Injection of Cellulose Ethers Administered Long before Infection Confers Sustained Protection against Prion Diseases in Rodents

“…However, daily oral administration of TC-5RW to intracerebrally infected animals was not effective, even if it was started before they contracted the infection (S6b Fig). This result may be due to the poor intestinal absorption of CEs [20]. …”

“…A single subcutaneous injection of TC-5RW (4 g/kg body weight) at 3 dpi extended the median survival times of animals by about 6.7-fold (97 days → 651.5 days) (Fig 2b). The results suggest that even a small amount of CE absorbed through the intestinal tract is effective over a long period of time in case of peripheral infection, although absorption of CEs in the intestinal tract is reportedly very limited when orally administered [20]. …”

The nonfermentable dietary fiber hydroxypropyl methylcellulose modulates intestinal microbiota

“…HPMC is considered to be not fermentable by gut microbiota in vitro (78) and consequently, is not absorbed. In a study administering 14 C‐radiolabeled HPMC to rats, 99% of the radioactivity was detected in the feces, 1% detected in the urine, and none detected in the tissues of the animal, demonstrating that HPMC does not undergo substantial degradation in the intestinal tract (46); thus, the way in which it alters the intestinal microbiota and improves health must differ from other commonly used prebiotic dietary fibers. The increases in fecal fats may be a primary source of microbiome perturbation; examination of similarly structured nonfermentable fibers may provide further insights.…”

“…The ability of HPMC to modulate the intestinal microbiota and maintain stable changes, whether due to a primary effect or to a secondary increase in fecal fats, indicates that it may be used as a prebiotic agent, able to reduce populations of specific microbes, including members of Lachnospiraceae (which contains common intestinal genera Blautia, Butyrivibrio, Coprococcus, Dorea, Johnsonella and Roseburia) and Ruminococcaceae (containing Faecalibacterium, Oscillospira, Ruminococcus, and Subdoligranulum), and induce the growth of specific microbes, such as members of Erysipelotrichaceae (containing Allobaculum, Coprobacillus, Holdemania, and Turicibacter) HPMC is considered to be not fermentable by gut microbiota in vitro (78) and consequently, is not absorbed. In a study administering 14 C-radiolabeled HPMC to rats, 99% of the radioactivity was detected in the feces, 1% detected in the urine, and none detected in the tissues of the animal, demonstrating that HPMC does not undergo substantial degradation in the intestinal tract (46); thus, the way in which it alters the intestinal microbiota and improves health must differ from other commonly used prebiotic dietary fibers. The increases in fecal fats may be a primary source of microbiome perturbation; examination of similarly structured nonfermentable fibers may provide further insights.…”

“…HPMC supplementation lowers cholesterol and postprandial insulin levels, in both rodents (15, 40, 41) and humans (16, 42, 43), and decreases weight gain (44) and fat mass (45) in rodents fed a high‐fat diet (HFD). HPMC is not absorbed by the host (46); however, it can modulate the intestinal nutrient environment by selectively increasing the excretion of fecal bile acids and fats (44) and increasing fecal water content (47), and thus have downstream effects on the intestinal microbiota.…”