Pharmacokinetics and ocular disposition of paracetamol and paracetamol glucuronide in rabbits with diabetes mellitus induced by alloxan

Background: this study evaluates the pharmacokinetics (pk) and ocular disposition of paracetamol and paracetamol glucuronide in diabetic rabbits. methods: thirty two new zealand rabbits were divided into four groups: control group (i,n = 8),control group with diabetes (ii,n = 8),rabbits with diabetes receiving paracetamol (iii,n = 8),rabbits without diabetes receiving paracetamol (iv,n = 8). to induce diabetes mellitus,alloxan was administrated intravenously (iv) in the dose of 90 mg/kg body weight (b.w.) to 16 rabbits (groups ii and iii). eight weeks post induction of the diabetic state,paracetamol was administrated via the ear vein at a dose of 35 mg/kg b.w. to groups iii and iv. blood and aqueous (ocular fluid) samples were collected after drug administration. pk calculations were made based on non-compartmental analysis. results: significant differences were observed in pk of paracetamol between the studied groups. lower value of the area under the concentration - time curve and enhanced clearance of paracetamol were noted in the diabetic group. in the case of paracetamol glucuronide,the area under the concentration - time curve was also little lower; however,no changes in the elimination rate were observed. simultaneously,diminished ocular disposition of paracetamol was obtained in the diabetic group,whereas no changes were noted according to the penetration of paracetamol glucuronide. conclusions: the pk as well as ocular disposition of paracetamol may be altered in non-treated diabetes mellitus the glucuronidation does not seem to be the process responsible for these changes. copyright © 2012 by institute of pharmacology polish academy of sciences.