The effect of acarbose on the pharmacokinetics of rosiglitazone.
OBJECTIVE
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.


CONCLUSIONS
Acarbose administered at therapeutic doses has a small, but clinically insignificant, effect on rosiglitazone pharmacokinetics.
Miller
A K
AK
SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19041, USA. Ann_K_Miller@sbphrd.com
Inglis
A M
AM
Culkin
K T
KT
Jorkasky
D K
DK
Freed
M I
MI
D020909:Acarbose / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D013844:Thiazoles / Q000493:pharmacokinetics*; D045162:Thiazolidinediones
D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D020909:Acarbose