The effect of acarbose on the pharmacokinetics of rosiglitazone

Abstract.

Objectives: To investigate whether treatment with acarbose alters the pharmacokinetics (PK) of coadministered rosiglitazone. Methods: Sixteen healthy volunteers (24–59-years old) received a single 8-mg dose of rosiglitazone on day 1, followed by 7 days of repeat dosing with acarbose [100 mg three times daily (t.i.d.) with meals]. On the last day of acarbose t.i.d. dosing (day 8), a single dose of rosiglitazone was given with the morning dose of acarbose. PK profiles following rosiglitazone dosing on days 1 and 8 were compared, and point estimates (PE) and associated 95% confidence intervals (CI) were calculated. Results: Rosiglitazone absorption [as measured with peak plasma concentration (C_max) and time to peak concentration (T_max)] was unaffected by acarbose. The area under the concentration–time curve from time zero to infinity [AUC_{(0– ∞ )}] was on average 12% lower (95% CI –21%, –2%) during rosiglitazone + acarbose coadministration and was accompanied by an approximate 1-h (23%) reduction in terminal elimination half-life t _1/2 (4.9 h versus 3.8 h). This small decrease in AUC_{(0– ∞ )} appears to be due to an alteration in systemic clearance of rosiglitazone and not changes in absorption. These observed changes in AUC_{(0– ∞ )} and t _1/2 are not likely to be clinically relevant. Coadministration of rosiglitazone and acarbose was well tolerated. Conclusion: Acarbose administered at therapeutic doses has a small, but clinically insignificant, effect on rosiglitazone pharmacokinetics.