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.
Highlights
Diabetes mellitus is a very commonly occurring metabolic disorder characterized by hyperglycemia and altered metabolism of lipids, proteins, and carbohydrates and occurs due to absolute or relative deficiency of insulin or insulin resistance.[1]
There is a close association between complications of diabetes and diabetic dyslipidemia
Drug interactions can lead to changed systemic exposure, resulting in variations in response of the coadministered drugs
Summary
Diabetes mellitus is a very commonly occurring metabolic disorder characterized by hyperglycemia and altered metabolism of lipids, proteins, and carbohydrates and occurs due to absolute or relative deficiency of insulin or insulin resistance.[1] Diabetes mellitus is associated with oxidative stress induced micro- and macrovascular complications. Long-term complications of diabetes mellitus involve almost all the vital organs such as heart, eyes, kidney, blood vessels, and nervous system. These complications lead to the development of obesity, hypertension, dyslipidemia, and insulin resistance.[2] There is a close association between complications of diabetes and diabetic dyslipidemia. Diabetic dyslipidemia accounts for around 80% diabetic deaths due to cardiovascular complications. There is a growing body of evidence to show that hyperglycemia and dyslipidemia are associated
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