In vivo and In vitro Drug Interactions Study of Glimepride with Atorvastatin and Rosuvastatin

Abstract

Aim of this investigation was to study the in vivo and in vitro drug interaction of glimepride with atorvastatin and rosuvastatin. In vitro drug interaction of glimepride with atorvastatin and rosuvastatin was studied using human pooled liver microsomes and evaluated using high performance liquid chromatography. In vivo pharmacokinetic drug interaction of glimepride (6 mg/kg) in coadministration with atorvastatin (60 mg/kg) and rosuvastatin (60 mg/kg) were studied in rats and analyzed using liquid chromatography tandem mass spectrometry (LC–MS/MS). In in vitro study, atorvastatin decreased its own metabolism as well as the metabolism of glimepiride. Rosuvastatin coadministration with glimepride reduced the metabolism of glimepride and increased the metabolism of its own. In in vivo study, concentration in plasma, Cmax, AUC(0–t) and AUC(0–∞) (area under the concentration-time curve, AUC) of glimepride was increased significantly in coadministration with atorvastatin whereas there was no significant change was observed in the case of coadministration with rosuvastatin. Half life (T1/2) and volume of distribution (Vd) of glimepride decreased significantly with both atorvastatin and rosuvastatin. Elimination rate constant, Kel of glimepride increased significantly with both atorvastatin and rosuvastatin. Clearance (Cl) of glimepride decreased significantly but the decrease was more with atorvastatin than with rosuvastatin. It is concluded that glimepride metabolism is little affected by rosuvastatin in vitro, which agreed with the negligible interaction in in vivo study. Thus, from safety point of view rosuvastatin is better to prescribe as a coadministration therapy with glimepiride. On the other hand, atorvastatin could cause an increase in the bioavailability of glimepride per oral and also significantly decrease the metabolism of glimerpride in in vitro study. This may pose a positive implication in clinical practice.

Synthesis and Spectroscopic Characterization of Metal Complexes of Rosuvastatin

“…The drug is soluble in methanol and ethanol. 26 It shows rapid solu bility in chloroform and DMSO. Its stability was checked by melting point (taking twice with the difference of two days.…”

“…26 From metabolic study of rosuvastatin it is clear that it majorly remains unchanged. 1 Literature survey reveals that CYP 2C9 enzymes metabolize it very minutely; even then it has shown interaction with some drugs with adverse effects.…”

Simultaneous Determination of Atorvastatin and Glimepiride by LC-MS/MS in Human Plasma and Its Application to a Pharmacokinetic Study

“…Harshini et al (2011) reported a method for simultaneous determination of ATV and GLI by HPLC [23]. Galani et al reported a in vitro and in vivo effect of GLI with rosuvastatin and ATV [4]. The objective of the present manuscript is to develop single, rapid and sensitive method for ATV and GLI that were reliably measure the analytes in the human plasma samples.…”

“…Atorvastatin (ATV)-Glimepiride (GLI) combines a competitive inhibitor of HMGCoA reductase and a sulfonylurea anti-diabetic drug GLI. In the references few bioanalytical methods were reported for the determination of ATV and GLI separately and in combination with another products [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Two methods have been reported for the simultaneous determination of ATV and GLI [22,23].…”

Pharmacokinetic interactions between glimepiride and rosuvastatin in healthy Korean subjects: does the <em>SLCO1B1</em> or <em>CYP2C9</em> genetic polymorphism affect these drug interactions?

“… 3 Especially, diabetic dyslipidemia attributes to ~80% of deaths due to cardiovascular complications. 4 It is necessary to treat dyslipidemia in patients with diabetes; 3 therefore, these patients are likely to take lipid-lowering drugs and antidiabetic drugs simultaneously. Thus, it is important to consider potential drug interactions between lipid-lowering drugs and antidiabetic drugs.…”