Pharmacokinetic and bioequivalence study of an oral 8 mg dose of rosiglitazone tablets in Thai healthy volunteers.

BACKGROUND: Rosiglitazone maleate is an antihyperglycemic agent in the thiazolidinedione class. It is indicated for the treatment of patients with type 2 diabetes mellitus. A new product of rosiglitazone has been developed. The pharmacokinetic in Thai subjects should be considered and the bioequivalent data of new generic product is required in order to assure the quality and performance. OBJECTIVE: To characterize the pharmacokinetics of rosiglitazone in Thai subjects and compare the bioequivalence of generic product of a single oral 8 mg rosiglitazone tablet with the innovator's product. MATERIAL AND METHOD: The present study was performed in 24 healthy Thai male volunteers. Each received a single oral dose of 8 mg rosiglitazone tablet. Double blind randomized two-way crossover design was used with two weeks washout period between treatments. After drug administration, a serial blood sample was collected over a period of 48 hours. Rosiglitazone plasma level was determined by HPLC with fluorescence detector. The pharmacokinetic parameters were determined by non compartment model. For bioequivalence determination, the difference of Cmax, AUC(0-t) and AUC(0-inf) were analyzed by ANOVA and 90% confidence interval. RESULTS: The mean +/- SD of pharmacokinetic parameters of generic product and the innovator's product were 0.82 +/- 0.52 vs. 1.02 +/- 1.50 hr of Tmax, 796.51 +/- 155.19 vs. 723.48 +/- 134.69 ng/ml of Cmax, 3.94 +/- 0.80 vs. 3.87 +/- 0.77 hr of T1/2, 4,308.43 +/- 1,006.28 vs. 4,135.66 +/- 1,061.96 ng x hr/ml of AUC(0-t), 4,384.65 +/- 1,035.15 vs. 4,183.87 +/- 1,075.39 ng x hr/ml of AUC(0-inf), respectively. The 90% confidence interval of mean difference of Cmax, AUC(0-t) and AUC(0-inf) (log transformed data) of generic product compared to the innovator's product were 98.42-122.18%, 97.28-109.66% and 97.79-110.30%, respectively. They were within the range of the acceptance criteria 80-125%. CONCLUSION: Pharmacokinetic parameters of a single oral dose of 8 mg rosiglitazone tablet were characterized in Thai healthy subjects. These parameters showed that rosiglitazone was rapidly absorbed with a short elimination half-life. The two formulations of rosiglitazone were bioequivalent.

A simple efficient technique of 'mid-dilution' on-line hemodiafiltration.

BACKGROUND: On-line hemodiafiltration (OL-HDF) with pre- as well as post-dilution reinfusion mode provides superior uremic toxin removal, especially middle uremic toxins, and can improve patient survival. Both standard pre- and post-dilution have limitations. Mid-dilution OL-HDF (Nephros OLpur) was invented to overcome the disadvantages of both standard modes, but such a cartridge is only available in limited centers and is expensive. METHODS: We created a simple technique of mid-dilution OL-HDF that can be easily set up in every hemodialysis center. Twelve stable end-stage renal disease patients were dialyzed in a random sequence with three different infusion modes of OL-HDF (simple mid-dilution, standard pre-dilution and post-dilution). Small molecule, middle molecule, and protein-bound uremic toxin clearances were measured. RESULTS: Simple mid-dilution OL-HDF provided high efficiency in uremic toxin clearances with less protein loss. CONCLUSION: Simple mid-dilution OL-HDF combines the advantages of pre- and post-dilution modes without adverse effects. Thus, this technique could be useful in decreasing morbidity and mortality in hemodialysis patients.