HPLC-DAD Method for Pharmacokinetic Interaction Study of Atorvastatin with Pioglitazone and Cholestyramine in Wistar Rats

Abstract

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.

A review on liquid chromatographic methods for the bioanalysis of atorvastatin

“…Most of the references cited in Tables 1 and 2 also describe the simultaneous determination of AT with certain other statins [13, 20, 24, 27-29, 50, 51, 54, 56, 61, 65, 81, 87] and other co-administered drugs such as amlodipine [35,40,59,64,65,69,70,77,78,95], ezetimibe [42,66,71], gemfibrozil [13,30,51], clopidogrel [14,15,41,93], fenofibrate [26], aspirin [15,23,72], ramipril [64,78], pioglitazone [17,22], glimepiride [64,68,73], olmesartan [62,98], and many other. Various methods have also been developed and validated using LC-MS/MS to quantify the metabolites of AT and are enlisted in Table 2 [54, 56-58, 60-62, 65, 67, 69, 70, 74-76, 79, 80, 82, 83, 85-91, 96, 100].…”

“…Various bioanalytical methods used LLE strategy for the sample pre-treatment of AT before the final analysis by using ethyl acetate, methyl-tertiary butyl ether, dichloromethane, or diethyl ether as organic extraction solvents. Instead of the single solvent procedure, various methods have also used a combination of different solvents [17,27,53,54,69,85,86] or various buffering agents such as FA [17,60]. AA [20] and phosphate buffer [33,[70][71][72]85] for the extraction of AT using LLE method.…”

Development and validation of a high throughput LC–MS/MS method for simultaneous quantitation of pioglitazone and telmisartan in rat plasma and its application to a pharmacokinetic study

“…Therefore, before going forward with this combination, the potential drug interactions of PIO and TLM in terms of pharmacokinetic perspective need to be studied. There are several bioanalytical methods exist for analysis of PIO [21] , [22] , [23] , [24] , [25] and TLM [26] , [27] , [28] either alone or in combination with other analytes in different types of biological matrices. But, to the best of our knowledge, there was no reported validated bioanalytical method for their simultaneous quantitation in any type of biological matrix.…”