TY - JOUR A2 - Chakrabarti, Subrata AU - Alkharfy, Khalid M. PY - 2009 DA - 2009/10/20 TI - Influence of Overt Diabetes Mellitus on Cyclosporine Pharmacokinetics in a Canine Model SP - 363787 VL - 2009 AB - 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 − 1 Kg − 1 versus 0.201 L hr − 1 Kg − 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. SN - 2314-6745 UR - https://doi.org/10.1155/2009/363787 DO - 10.1155/2009/363787 JF - Experimental Diabetes Research PB - Hindawi Publishing Corporation KW - ER -