### Absorption

In a study of 6 healthy men, less than 2% of an oral dose of acarbose was absorbed as active drug, while approximately 35% of total radioactivity from a 14C-labeled oral dose was absorbed. An average of 51% of an oral dose was excreted in the feces as unabsorbed drug-related radioactivity within 96 hours of ingestion. Because acarbose acts locally within the gastrointestinal tract, this low systemic bioavailability of parent compound is therapeutically desired. Following oral dosing of healthy volunteers with 14C-labeled acarbose, peak plasma concentrations of radioactivity were attained 14–24 hours after dosing, while peak plasma concentrations of active drug were attained at approximately 1 hour. The delayed absorption of acarbose-related radioactivity reflects the absorption of metabolites that may be formed by either intestinal bacteria or intestinal enzymatic hydrolysis.

### Metabolism

Acarbose is metabolized exclusively within the gastrointestinal tract, principally by intestinal bacteria, but also by digestive enzymes. A fraction of these metabolites (approximately 34% of the dose) was absorbed and subsequently excreted in the urine. At least 13 metabolites have been separated chromatographically from urine specimens. The major metabolites have been identified as 4-methylpyrogallol derivatives (that is, sulfate, methyl, and glucuronide conjugates). One metabolite (formed by cleavage of a glucose molecule from acarbose) also has alpha-glucosidase inhibitory activity. This metabolite, together with the parent compound, recovered from the urine, accounts for less than 2% of the total administered dose.

### Excretion

The fraction of acarbose that is absorbed as intact drug is almost completely excreted by the kidneys. When acarbose was given intravenously, 89% of the dose was recovered in the urine as active drug within 48 hours. In contrast, less than 2% of an oral dose was recovered in the urine as active (that is, parent compound and active metabolite) drug. This is consistent with the low bioavailability of the parent drug. The plasma elimination half-life of acarbose activity is approximately 2 hours in healthy volunteers. Consequently, drug accumulation does not occur with three times a day (t.i.d.) oral dosing.

### Special Populations

The mean steady-state area under the curve (AUC) and maximum concentrations of acarbose were approximately 1.5 times higher in elderly compared to young volunteers; however, these differences were not statistically significant. Patients with severe renal impairment (Clcr < 25 mL/min/1.73m2) attained about 5 times higher peak plasma concentrations of acarbose and 6 times larger AUCs than volunteers with normal renal function. No studies of acarbose pharmacokinetic parameters according to race have been performed. In U.S. controlled clinical studies of PRECOSE in patients with type 2 diabetes mellitus, reductions in glycosylated hemoglobin levels were similar in Caucasians (n=478) and African-Americans (n=167), with a trend toward a better response in Latinos (n=132).

### Drug-Drug Interactions

Studies in healthy volunteers have shown that PRECOSE has no effect on either the pharmacokinetics or pharmacodynamics of nifedipine, propranolol, or ranitidine. PRECOSE did not interfere with the absorption or disposition of the sulfonylurea glyburide in diabetic patients. PRECOSE may affect digoxin bioavailability and may require dose adjustment of digoxin by 16% (90% confidence interval: 8-23%), decrease mean Cmaxof digoxin by 26% (90% confidence interval: 16–34%) and decreases mean trough concentrations of digoxin by 9% (90% confidence limit: 19% decrease to 2% increase). (See PRECAUTIONS, Drug Interactions.)

The amount of metformin absorbed while taking PRECOSE was bioequivalent to the amount absorbed when taking placebo, as indicated by the plasma AUC values. However, the peak plasma level of metformin was reduced by approximately 20% when taking PRECOSE due to a slight delay in the absorption of metformin. There is little if any clinically significant interaction between PRECOSE and metformin.