The effect of acarbose on the pharmacokinetics of rosiglitazone

Autor: Martin I. Freed, Anne Marie L. Inglis, Ann K. Miller, Diane K. Jorkasky, Kathleen Thompson Culkin
Rok vydání: 2001
Předmět:
Zdroj: European journal of clinical pharmacology. 57(2)
ISSN: 0031-6970
Popis: 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–∞)] 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–∞) appears to be due to an alteration in systemic clearance of rosiglitazone and not changes in absorption. These observed changes in AUC(0–∞) 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.
Databáze: OpenAIRE
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