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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

RP-HPLC chromatograms at 260 nm spiked with ISTD (valsartan) A: LQC; B: in vivo plasma sample obtained after 1.0 h from Wistar rats dosed with atorvastatin and pioglitazone; C: blank rat plasma
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Figure 2: RP-HPLC chromatograms at 260 nm spiked with ISTD (valsartan) A: LQC; B: in vivo plasma sample obtained after 1.0 h from Wistar rats dosed with atorvastatin and pioglitazone; C: blank rat plasma

Mentions: Trials were performed during optimization and some important parameters i.e. pH of the mobile phase, concentration of the acid or buffer solution, percentage and type of the organic modifier, different columns, and flow rates etc. were tested for a good chromategraphic separation of pioglitazone hydrochloride, atorvastatin calcium, and ISTD (valsartan) individually. Trials showed that the acidic mobile phase with a reversed-phase C18 column gives symmetric and sharp peaks. For this reason, 10 mM ammonium formate solution was preferred as the acidic buffer solution. Methanol was not sufficient to resolve the drug, so we introduced acetonitrile considering its high eluting power. The final mobile composition was 48% methanol, 19% acetonitrile, and 33% 10 mM ammonium formate (pH 3.5±0.2) run over 15 minute periods with a 1 ml/min flow rate. Retention times under these conditions were 7.26, 8.87, and 11.29 for PIO, ISTD, and ATR, respectively (Fig. 2). For the quantitative analytical purpose, the 260 nm wavelength was selected over the array of wavelengths obtained by the diode array detector due to decreased interferences.


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

Sharma RN, Pancholi SS - Sci Pharm (2014)

RP-HPLC chromatograms at 260 nm spiked with ISTD (valsartan) A: LQC; B: in vivo plasma sample obtained after 1.0 h from Wistar rats dosed with atorvastatin and pioglitazone; C: blank rat plasma
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: RP-HPLC chromatograms at 260 nm spiked with ISTD (valsartan) A: LQC; B: in vivo plasma sample obtained after 1.0 h from Wistar rats dosed with atorvastatin and pioglitazone; C: blank rat plasma
Mentions: Trials were performed during optimization and some important parameters i.e. pH of the mobile phase, concentration of the acid or buffer solution, percentage and type of the organic modifier, different columns, and flow rates etc. were tested for a good chromategraphic separation of pioglitazone hydrochloride, atorvastatin calcium, and ISTD (valsartan) individually. Trials showed that the acidic mobile phase with a reversed-phase C18 column gives symmetric and sharp peaks. For this reason, 10 mM ammonium formate solution was preferred as the acidic buffer solution. Methanol was not sufficient to resolve the drug, so we introduced acetonitrile considering its high eluting power. The final mobile composition was 48% methanol, 19% acetonitrile, and 33% 10 mM ammonium formate (pH 3.5±0.2) run over 15 minute periods with a 1 ml/min flow rate. Retention times under these conditions were 7.26, 8.87, and 11.29 for PIO, ISTD, and ATR, respectively (Fig. 2). For the quantitative analytical purpose, the 260 nm wavelength was selected over the array of wavelengths obtained by the diode array detector due to decreased interferences.

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