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

Sharma RN, Pancholi SS - Sci Pharm (2014)

Bottom Line: The combination of atorvastatin and pioglitazone was found to be effective in reducing the thickness of the carotid intima-media layer.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.

View Article: PubMed Central - PubMed

Affiliation: Shree S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Mehsana-Gojaria Highway, Gujarat, 382014, India.

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.

No MeSH data available.


Related in: MedlinePlus

Peak purity curve of A. pioglitazone, B. internal standard, and C. atorvastatin by the diode array detector (DAD)
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Figure 3: Peak purity curve of A. pioglitazone, B. internal standard, and C. atorvastatin by the diode array detector (DAD)

Mentions: No endogenous source of interference was observed at the retention times of the analytes in any of the six lots of plasma when a comparison of the blank and QC level samples was made. Typical chromatograms obtained from the blank plasma and plasma samples containing the LQC of PIO and ATR are presented in Figure 2A. Also, the peak purity plots for PIO, ATR, and ISTD showed peak purity indices of nearly 1 for each and no other peaks were co-eluted with the analytes (Fig. 3).


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

Sharma RN, Pancholi SS - Sci Pharm (2014)

Peak purity curve of A. pioglitazone, B. internal standard, and C. atorvastatin by the diode array detector (DAD)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4318181&req=5

Figure 3: Peak purity curve of A. pioglitazone, B. internal standard, and C. atorvastatin by the diode array detector (DAD)
Mentions: No endogenous source of interference was observed at the retention times of the analytes in any of the six lots of plasma when a comparison of the blank and QC level samples was made. Typical chromatograms obtained from the blank plasma and plasma samples containing the LQC of PIO and ATR are presented in Figure 2A. Also, the peak purity plots for PIO, ATR, and ISTD showed peak purity indices of nearly 1 for each and no other peaks were co-eluted with the analytes (Fig. 3).

Bottom Line: The combination of atorvastatin and pioglitazone was found to be effective in reducing the thickness of the carotid intima-media layer.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.

View Article: PubMed Central - PubMed

Affiliation: Shree S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Mehsana-Gojaria Highway, Gujarat, 382014, India.

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.

No MeSH data available.


Related in: MedlinePlus