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Tharandt et al. (1979) evaluated the absorption, distribution, metabolism, and excretion of D-glucono-δ-lactone and sodium-D-gluconate in a series of experiments conducted in Wistar rats.  The compound D-glucono-δ-lactone was shown to be rapidly absorbed, utilized in the pentose phosphate pathway, and incorporated into liver glycogen. The intestinal absorption of D-glucono-δ-lactone and of sodium-D-gluconate was rapid following oral administration with a higher degree of absorption reported for the lactone.  Following the oral administration of D-glucono-δ-lactone and sodium-D-gluconate, excretion occurred via the feces, urine, and expired air.  The volume of distribution was determined to be 50.55 and 40.97% of the total body weight for D-glucono-δ-lactone and sodium-D-gluconate, respectively. Based on the results of this study, the bioaccumulation potential of D-glucono-δ-lactone and sodium-D-gluconate cannot be determined.

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 In one experiment, D-glucono-δ-lactone (in combination with 20% Tris w/w) was orally administered to fasted healthy male rats at a single dose of 4 g/kg body weight to assess and compare the absorption of the compound and its subsequent incorporation into hepatic glycogen stores. D-glucono-δ-lactone is commonly believed to be metabolized to gluconic acid and lactone, which are intermediates in the oxidation of glucose through the pentose phosphate cycle. Liver samples were excised, and the levels of glycogen metabolites (glucose-6-phosphate and 6-phosphogluconate) were measured in groups of animals 5 hours following administration of D-glucono-δ-lactone. The measured levels of hepatic glucose-6-phosphate and 6-phosphogluconate 5 hours following administration of D-glucono-δ-lactone were 163 and 27 µmol/kg wet weight, respectively, similar to normal (i.e., untreated and fed) animals. Thus, the results of this experiment support the absorption, distribution to the liver, and incorporation into the pentose phosphate pathway of D-glucono-δ-lactone in healthy male rats. Of note, although D-glucono-δ-lactone is readily hydrolyzed to gluconic acid, the addition of 20% Tris buffer stabilized the lactone ring of D-glucono-δ-lactone, thus increasing the absorption of the intact compound. The authors noted that liver glycogen levels were greatest when D-glucono-δ-lactone, which is normally hydrolyzed in aqueous solution, was administered along with a 20% Tris buffer (w/w). 

 

In a second experiment, radiolabelled D-glucono-δ-lactone and sodium-D-gluconate were orally administered to fasted healthy male rats at single dosages of 0.8 g/kg body weight to compare its absorption, distribution, and excretion. Five hours after administration, radioactivity was measured in the feces and intestines, urine, exhaled carbon dioxide, and whole body (excluding the gastrointestinal tract) of the test animals. Radioactivity was also measured in blood samples. The amounts of radioactivity recovered from exhaled carbon dioxide, the whole body (excluding the gastrointestinal tract), the intestine and feces, and the urine following the administration of radiolabelled D-glucono-δ-lactone represented 25.0, 23.1, 29.5, and 7.0% of the administered dose, respectively. These results indicated that at least 70.5% (i.e., the remaining proportion of the dose after subtracting the amount recovered from the intestine and feces) of the dose of radiolabelled D-glucono-δ-lactone was absorbed following oral administration. The total recovered radioactivity of D-glucono-δ-lactone was reported to be approximately 84.6% of the dose. The radioactivity of sodium-D-gluconate was reported to be 12.1, 19.7, 44.9, and 5.0% from exhaled carbon dioxide, from the whole body (excluding the gastrointestinal tract), intestine and feces, and in the urine, respectively after 5 hours. The total recovered radioactivity of sodium-D-gluconate was reported to be approximately 81.7% of the dose. These results suggested that at least 55.1% of the dose of radiolabelled sodium-D-gluconate was absorbed after oral administration. According to the results observed in the blood, feces, and intestine, the authors reported rapid intestinal absorption following the oral administration of D-glucono-δ-lactone and that D-glucono-δ-lactone was absorbed to a greater degree than sodium D-gluconate.

 

In a third experiment, a single dose of radiolabelled D-glucono-δ-lactone or sodium-D-gluconate (0.655 μCi) was intravenously injected in healthy male rats to assess the volume of distribution. Five minutes following administration, gluconate and, even more so, D-glucono-δ-lactone were detected in considerable amounts intracellularly (exact amounts and specific tissues assessed not reported). Approximately 0.18 and 0.51% of the applied dose of sodium-D-gluconate and D-glucono-δ-lactone, respectively, was retained in the liver glycogen. The authors determined the volume of distribution of sodium-D-gluconate and D-glucono-δ-lactone to be 40.97 and 50.11% of the total body weight in rats, respectively.