Sharma Ritesh N, Pancholi Shyam S
Shree S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Mehsana-Gojaria Highway, Gujarat, 382014, India.
Babria Institute of Pharmacy, Vadodara, 391240, Gujarat, India.
Sci Pharm. 2014 Mar 13;82(3):555-70. doi: 10.3797/scipharm.1401-18. Print 2014 Jul-Sep.
Carotid intima-media thickness is used as a surrogate marker for cardiovascular complications in diabetes mellitus. The combination of atorvastatin and pioglitazone was found to be effective in reducing the thickness of the carotid intima-media layer. The method of RP-HPLC coupled with a diode array detector (DAD) was developed for the pharmacokinetic interaction study of atorvastatin with pioglitazone and cholestyramine, respectively, in Wistar rats. Atorvastatin (ATR) and pioglitazone (PIO) were resolved on a C18 column with a mobile phase composed of 48% methanol, 19% acetonitrile, and 33% 10 mM ammonium formate (v/v/v; pH 3.5±0.3, by formic acid) and a 260 nm detection wavelength on the diode array detector. The method was validated according to international standards with good reproducibility and linear response; mean (r) 0.9987 and 0.9972 to ATR and PIO, respectively. The coefficients of variation of intra- and interassay precision ranged between 4.95-8.12 and 7.29-9.67, respectively. Pharmacokinetic parameters were determined in rats following an oral administration of atorvastatin in the presence and absence of pioglitazone and also with cholestyramine. Compared with the control given atorvastatin alone, the Cmax and AUC of atorvastatin were merely unchanged in rats with the co-administration of pioglitazone, while they decreased by nearly 21 and 15%, respectively, with the concurrent use of cholestyramine. There were no significant changes in Tmax and the plasma half-life (T1/2 ) of atorvastatin in both cases. The performed experiment demonstrated that the presented method was suitable for the estimation and pharmacokinetic interaction study of atorvastatin with pioglitazone and cholestyramine in Wistar rat plasma.
颈动脉内膜中层厚度被用作糖尿病心血管并发症的替代标志物。已发现阿托伐他汀和吡格列酮联合使用可有效降低颈动脉内膜中层厚度。开发了反相高效液相色谱法结合二极管阵列检测器（DAD），分别用于研究阿托伐他汀与吡格列酮和考来烯胺在Wistar大鼠体内的药代动力学相互作用。阿托伐他汀（ATR）和吡格列酮（PIO）在C18柱上分离，流动相由48%甲醇、19%乙腈和33% 10 mM甲酸铵（v/v/v；pH 3.5±0.3，用甲酸调节）组成，二极管阵列检测器的检测波长为260 nm。该方法按照国际标准进行了验证，具有良好的重现性和线性响应；对ATR和PIO的平均（r）分别为0.9987和0.9972。批内和批间精密度的变异系数分别在4.95 - 8.12和7.29 - 9.67之间。在有和没有吡格列酮以及有考来烯胺存在的情况下，给大鼠口服阿托伐他汀后测定药代动力学参数。与单独给予阿托伐他汀的对照组相比，联合使用吡格列酮时，大鼠体内阿托伐他汀的Cmax和AUC仅无变化，而同时使用考来烯胺时，它们分别下降了近21%和15%。在这两种情况下，阿托伐他汀的Tmax和血浆半衰期（T1/2）均无显著变化。所进行的实验表明，该方法适用于Wistar大鼠血浆中阿托伐他汀与吡格列酮和考来烯胺的测定及药代动力学相互作用研究。
