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 (Cmax) and time to peak concentration (Tmax)] was unaffected by acarbose. The area under the concentration-time curve from time zero to infinity [AUC(0-infinity)] 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 t1/2 (4.9 h versus 3.8 h). This small decrease in AUC(0-infinity) appears to be due to an alteration in systemic clearance of rosiglitazone and not changes in absorption. These observed changes in AUC(0-infinity) and t1/2 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.
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 (Cmax) and time to peak concentration (Tmax)] was unaffected by acarbose. The area under the concentration-time curve from time zero to infinity [AUC(0-infinity)] 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 t1/2 (4.9 h versus 3.8 h). This small decrease in AUC(0-infinity) appears to be due to an alteration in systemic clearance of rosiglitazone and not changes in absorption. These observed changes in AUC(0-infinity) and t1/2 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.
Authors: Bardia Askari; Jenny E Kanter; Ashley M Sherrid; Deidre L Golej; Andrew T Bender; Joey Liu; Willa A Hsueh; Joseph A Beavo; Rosalind A Coleman; Karin E Bornfeldt Journal: Diabetes Date: 2007-01-26 Impact factor: 9.461
Authors: Ya Xu; Michael Gen; Li Lu; Jennifer Fox; Sara O Weiss; R Dale Brown; Daniel Perlov; Hasan Ahmad; Peili Zhu; Clifford Greyson; Carlin S Long; Gregory G Schwartz Journal: Am J Physiol Heart Circ Physiol Date: 2004-11-04 Impact factor: 4.733