Influence of Overt Diabetes Mellitus on Cyclosporine Pharmacokinetics in a Canine Model

Abstract

Background/Aims. Diabetic patients usually require more medications than their nondiabetic counterparts. This work examined the effect of hyperglycemia on the pharmacokinetic properties of cyclosporine in a diabetic dog model.Main Methods. Diabetes was induced using a streptozotocin/alloxan combination and verified by measuring the serum glucose level. Cyclosporine was administered as a bolus intravenous dose of 5 mg/kg, and blood samples were collected at different time points for determining drug concentrations and biochemical analyses.Results. Diabetic dogs showed a significant increase in total body clearance of cyclosporine compared to healthy controls (0.457 L versus 0.201 L , ) and a decrease in its biological half-life (9.32 hours versus 22.56 hours, ). In addition, diabetic animals exhibited a higher total cholesterol ( mmol/L and  mmol/L; ) as well as more serum low density lipoproteins ( mmol/L versus  mmol/L; ).Conclusion. Overt diabetes alters cyclosporine disposition by modulating its clearance. Abnormalities in the lipid profile, among other factors, may contribute to the accelerated metabolic degradation of cyclosporine under hyperglycemic conditions.