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  • Title: Disposition of 14C-alpha-cyclodextrin in germ-free and conventional rats.
    Author: Van Ommen B, De Bie AT, Bär A.
    Journal: Regul Toxicol Pharmacol; 2004 Jun; 39 Suppl 1():57-66. PubMed ID: 15265616.
    Abstract:
    The absorption, disposition, metabolism, and excretion of uniformly (14)C-labeled alpha-cyclodextrin ((14)C-alpha-CD) was examined in four separate experiments with Wistar rats. In Experiment 1, (14)C-alpha-CD (25 microCi, 50 mg/kg bw) was administered intravenously to four male and four female conventional rats. In Experiment 2, (14)C-alpha-CD (25 microCi, 200 mg/kg bw) was given by gavage to four male and four female germ-free rats. In Experiments 3 and 4, (14)C-alpha-CD was given to groups of four male and four female conventional rats by gavage at different dose levels (100 microCi, 200 mg/kg bw; 25 microCi, 200 and 100 mg/kg bw). In all experiments, (14)C was measured in respiratory CO(2), urine, and feces over periods of 24-48 h, and in the contents of the gastrointestinal tract, blood, main organs, and residual carcass at termination of the experiments. The chemical identity of the (14)C-labeled compounds was examined by HPLC in blood (Experiment 1), urine (Experiments 1-4), feces (Experiments 2-4), and samples of intestinal contents (Experiments 2 and 4). Recovered (14)C was expressed as percentage of the administered dose. Experiment 1 showed that intravenously administered alpha-CD is excreted rapidly with urine. During the first 2h after dosing, plasma (14)C levels decreased rapidly (t(1/2), 26 and 21 min in male and female rats, respectively). About 13% of the administered (14)C dose (range 4.6-30.6) was detected in the feces, respiratory CO(2), organs, and carcass at the end of the experiment, i.e., 24 h after dosing. The presence of about 1.9% in the intestinal contents and feces suggests that a certain fraction of systemic alpha-CD is eliminated with the bile or saliva. Conclusive evidence, either positive or negative, for a hydrolysis and further metabolism of a small fraction of the administered alpha-CD by the enzymes of the mammalian body could not be gained from this experiment. Upon oral administration of (14)C-alpha-CD to germ-free rats (Experiment 2), about 1.3% of the label expired as CO(2) within 24 h. In the urine collected from 0 to 8 h after dosing, (14)C-alpha-CD was the only radiolabeled compound detected. The amounts of alpha-CD detected in the urine suggest that on average about 1% of an oral dose is absorbed in rats during small-intestinal passage. In conventional rats (Experiments 3 and 4), a delayed appearance of respiratory (14)CO(2) was observed which is attributed to the non-digestibility of alpha-CD and its subsequent microbial fermentation in the cecum and colon. In the urine collected at 4 h after dosing, a small amount of unchanged (14)C-alpha-CD was detected which confirms that about 1% of the ingested alpha-CD is absorbed intact and is excreted via the kidneys. No (14)C-alpha-CD was found in the feces. It is concluded from the data that ingested (14)C-alpha-CD is not digested in the small intestine of rats but is fermented completely by the intestinal microbiota to absorbable short-chain fatty acids. Therefore, the metabolism of alpha-CD resembles closely that of resistant starch or other fermentable dietary fibers.
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