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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

Structures of atorvastatin (A), pioglitazone (B), and Valsartan (C, ISTD)
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Figure 1: Structures of atorvastatin (A), pioglitazone (B), and Valsartan (C, ISTD)

Mentions: Atorvastatin (ATR) is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, which in turn lowers the cholesterol and lipoprotein levels in the body [7]. ATR is chemically [R-(R*,R*)]-2-(4-fluorophenyl)-ß, δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, calcium salt (2:1) trihydrate (Fig. 1A) [8]. Atorvastatin, after oral administration in its active acidic form, is rapidly absorbed and undergoes extensive first-pass metabolism mainly by cytochrome P450 3A4 (CYP3A4) in the liver [9], which results in ortho- and para-hydroxylated derivatives and various beta-oxidation products [10]. Elimination of the drug is mainly through the bile following hepatic and/or extra-hepatic metabolism, and the mean plasma half-life of ATR is 14 hr [11].


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

Sharma RN, Pancholi SS - Sci Pharm (2014)

Structures of atorvastatin (A), pioglitazone (B), and Valsartan (C, ISTD)
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Structures of atorvastatin (A), pioglitazone (B), and Valsartan (C, ISTD)
Mentions: Atorvastatin (ATR) is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, which in turn lowers the cholesterol and lipoprotein levels in the body [7]. ATR is chemically [R-(R*,R*)]-2-(4-fluorophenyl)-ß, δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, calcium salt (2:1) trihydrate (Fig. 1A) [8]. Atorvastatin, after oral administration in its active acidic form, is rapidly absorbed and undergoes extensive first-pass metabolism mainly by cytochrome P450 3A4 (CYP3A4) in the liver [9], which results in ortho- and para-hydroxylated derivatives and various beta-oxidation products [10]. Elimination of the drug is mainly through the bile following hepatic and/or extra-hepatic metabolism, and the mean plasma half-life of ATR is 14 hr [11].

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