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 (i.e., 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 Cmax of 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.

Clinical Trials

Clinical Experience from Dose Finding Studies in Type 2 Diabetes Mellitus Patients on Dietary Treatment Only: Results from six controlled, fixed-dose, monotherapy studies of PRECOSE® in the treatment of type 2 diabetes mellitus, involving 769 PRECOSE®-treated patients, were combined and a weighted average of the difference from placebo in the mean change from baseline in glycosylated hemoglobin (HbA1c) was calculated for each dose level as presented below:

Table 1: Mean Placebo-Subtracted Change in HbA1c in Fixed-Dose Monotherapy Studies

Bookmark this page: