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

الملخص EN

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 hr−1Kg−1 versus 0.201 L hr−1Kg−1, P=.0019) and a decrease in its biological half-life (9.32 hours versus 22.56 hours, P=.0125).

In addition, diabetic animals exhibited a higher total cholesterol (7.20±0.62 mmol/L and 5.28±0.36 mmol/L; P<.05) as well as more serum low density lipoproteins (4.45±0.72 mmol/L versus 1.06±0.10 mmol/L; P<.05).

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.