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Abstract
Pharmacokinetics, biodistribution, and excretion of the α-glucosidase inhibitor and antiviral compound N-benzyl-1-deoxynojiri-mycin (BndNM) were studied in mice, after intravenous, subcutaneous, and oral administration of a single radiolabeled dose. No metabolites were detected in plasma, urine, or feces extracts. BndNM, a lipophilic derivative of 1-deoxynojirimycin (dNM), showed a biexponential plasma decay with an initial half-life (t1/2) of 9 min and an apparent terminal t1/2 of 62 min. The mean bioavailability was 89% after subcutaneous and on the average 82% after oral dosing to fed mice. Decay curves of BndNM in plasma and total blood coincided exactly for all routes of administration, indicating equal concentrations in plasma and blood cells. Tissue concentrations of BndNM were higher than plasma concentrations at all time points (0.5-24 h) in all collected tissues (kidney, liver, large and small intestines, and stomach) but especially in kidney, where tissue/plasma concentration ratios of 10 to 15 were reached. Only small amounts of BndNM were recovered from collected gallbladders, not exceeding 0.1 % of the dose. Recovery of BndNM in urine and feces was quite similar to that of N-methyl-dNM, a more hydrophilic dNM derivative that is not metabolized either. After 24 h., only small fractions of the dose of BndNM were recovered from feces: 1.2% after subcutaneous dosing, 4.2% after oral dosing, and 4.9% after intravenous dosing. Much higher amounts were recovered from the urine: 91% of the dose after subcutaneous administration, 89% after oral dosing, and 75% after intravenous injection. It is concluded that elimination including tubular secretion represents the major elimination route for BndNM and that significant tissue retention of the drug occurs even 24 h after administration.