Effects of Yukmijihwang-tang, a Polyherb, on the Pharmacokinetics of Metformin.

Metformin is one of the most common medicines for the treatment of type 2 diabetes, however, recent studies suggest that concomitant antihyperglycemic agents should be administered for better efficacy. Yukmijihwang-tang (YMJHT) is a nephroprotective polyherb prescribed for renal disorders or diabetic mellitus in traditional Korean medicine. Therefore, the pharmacokinetics between metformin and YMJHT were examined for their coadministration. Rats were orally coadministered with metformin and YMJHT as a combination group or metformin and distilled water as the corresponding control. Then, the metformin concentration in plasma and its pharmacokinetic parameters including maximum concentration (Cmax) and area under the plasma concentration time curve (AUC) were analyzed. There were no interactions between metformin and YMJHT in the single coadministration at intervals within 5 min. However, pretreatments with YMJHT for 6 days increased the metformin concentration and its Cmax and AUC (p<0.05). The repeated coadministration for 8 days increased the Cmax of metformin (p<0.05). Conversely, when the combination was coadministered at 2h -intervals, there were no interactions between metformin and YMJHT after a single dosing or repeated dosing of coadministration for 7 days. These results of the present study will help structure proper dosing regimens for the concomitant therapy of metformin and YMJHT.

Effects of Chungsinoryungsan, a polyherbal complex, on the pharmacokinetic profiles of perindopril in rats.

For sufficient antihypertension with less adverse effects, numerous clinical trials have recommended combination therapy using two or more hypertensive drugs. Chungsinoryungsan (CSORS) is a polyherbal complex based on oriental medicine, which has shown therapeutic potentials for antihypertension and additional renal improvement. Therefore, the affect of CSORS on the pharmacokinetic profiles of perindopril, an antihypertensive drug, was analyzed as a novel combination of hypertensive drugs. Rats received perindopril with CSORS as the combination or distilled water as the control. The co-administration of perindopril with CSORS or distilled water was performed by single dosing or repeated dosing for a week at a 2-h interval. The analyzed pharmacokinetic parameters included peak concentration (Cmax), time to reach the Cmax (Tmax), area under the plasma concentration-time curve, terminal half-life (t1/2) and mean residence time to infinity (MRTinf). In the single oral co-administration within 5 min, the pharmacokinetics of perindopril demonstrated an increased Tmax and MRTinf but reduced t1/2 in the combination compared to the control treatment, indicating drug-drug interactions between perindopril and CSORS. However, in the repeated co-administration for a week at a 2-h interval, which was more than perindopril MRTinf in the control treatment (1.5±0.1 h), the initial co-administration showed no differences in the pharmacokinetics between the combination and control treatments. Furthermore, the repeated co-administration also showed no differences between the combination and control treatment. The results indicate that CSORS can be co-administered at a 2-h interval that was more than perindopril MRTinf and further clinical studies may provide detailed information for developing a drug regimen that generates enhanced combination effects of CSORS with hypertensive drugs.

Total knee arthroplasty without patellar resurfacing.

One hundred and eleven total knee replacements without patellar resurfacing were followed-up for a minimum of 48.8 months (range 48.8-108.2 months; average 78.2 months). Evaluation was performed using the Knee Society Clinical Rating System (KS-CRS). Preoperatively, the mean knee score was 34.3 points and the mean function score was 42.2 points. Postoperatively, this knee score improved to a mean of 91.1 points and the function score improved to mean of 89.6 points at the most recent follow-up. There were no significant differences among the knees with mild, moderate, or severe degenerative change to the patella with regard to the preoperative (p=0.83) and postoperative (p=0.39) knee pain score. It seems likely that the postoperative knee pain is not related to the severity of degenerative change to the patella in total knee arthroplasties performed without patellar resurfacing, and none of those patients required patellar resurfacing to achieve knee pain relief.