背景及目的
Nimesulide是一種cyclooxygenase-2(COX-2)抑制劑,具有鎮痛解熱及抑制血小板弁鄋漁蘆G。COX-2抑制劑被認為具有較少的腸胃方面之副作用。但近年來有心臟方面之不良反應之報告,而被留意。因藥品在不同的種族間可能有不同的藥物動力反應,因而本研究的目的是比較台灣人和西方人在口服nimesulide後的藥物動力參數,以評估是否在台灣人使用時,是否有調整劑量的必要。
方法
有十二位志願者,年齡在25到39歲之間,完成此研究。每位受試者在經過一個晚上的禁食後,口服一顆100mg的nimesulide。血液樣品收集時間直到24小時。血中藥物濃度以HPLC來偵測。而藥物動力參數以血中濃度─時間關係求得。
結果
在健康之台灣志願者口服100mg的nimesulide後,平均AUC0-∞為59.27±22.78μg‧h/ml,為西方人的1.14到3.73倍。Cmax為6.09±1.10μg/ml為西方人的0.94到2.13倍。清除率為西方人的31.0%到71.7%之間。綜合此結果及文獻資料,顯示台灣人較西方人有較高之Cmax、AUC0-∞,較低的清除率及較低的volume distribution。而Tmax及t1/2則和西方人差異不大。
結論
台灣人口服nimesulide的藥物動力參數可能和西方人不同,我們需更多的藥物動力學,藥效學及藥物基因學之研究,來確定台灣人使用此藥時之最佳劑量。 Background and purpose
Nimesulide is a selective cyclooxygenase-2 (COX-2) inhibitor exerting analgesic, antipyretic and antiplatelet activity. COX-2 inhibitor was shown to have less gastrointestinal adverse effects. However, its cardiovascular side effect has been drawn much attention recently. The purpose of the study is to compare the pharmacokinetics of nimesulide(via oral administration) in Taiwanese subjects to that of Western peoples.
Methods
Twelve healthy Taiwanese subjects (25 to 39 years) enrolled in the study. Each subject received a single oral dose of 100mg numesulide in fasting state. After orally administrated, blood samples were drawn up to 24 hours. The plasma concentrations of nimesulide were determined using HPLC and pharmacokinetic parameters were derived from nimesulide plasma concentration-time profiles..
Results
Following oral administration of 100mg nimesulide in Taiwanese subjects, the AUC0-∞was 59.27±22.78μg‧h/ml, which is 1.14 to 3.73 times to the results in Western peoples. The Cmax was 6.09±1.10μg/ml, which is 0.94 to 2.13 times higher compared to the results of Western peoples. Clearance in Taiwanese was only 31.0 to 71.7% compared to the clearance of Western groups. Both data as well as previous publication, showed taht higher Cmax , AUC and lower clearance, lower volume distribution in Taiwanese subjects were observed compared to those in Western people. Tmax and t1/2 did not differ significantly between Taiwanese and Western people.
Conclusion:
The pharmacokinetics parameters of nimesulide in Taiwanese subjects may be different from other ethnic populations. More pharmacokinetic and pharmcodynamic studies are needed to determine the optimal dosage of nimesulide for Taiwanese.