Pharmacokinetics and ocular disposition of paracetamol and paracetamol glucuronide in rabbits with diabetes mellitus induced by alloxan.
Journal Title: Pharmacological Reports - Year 2012, Vol 64, Issue 2
Abstract
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.
Authors and Affiliations
Agnieszka Bienert, Jan Olszewski, Joanna Gracz, Tomasz Grabowski, Anna Wolc, Edmund Grześkowiak
Keywords
Related Articles
- EP ID EP140404
- DOI -
- Views 128
- Downloads 0
Ethanol withdrawal-induced depressive symptoms in animals and therapeutic potential of sigma1 receptor ligands.
Clinical evidence has indicated a high degree of comorbidity of alcoholism and depression. Manifestation of the depression symptoms during abstinence increases the likelihood of relapse and indicates a worse prognosis in...
Neurochemical modulation of stress-induced cognitive inflexibility in a rat model of an attentional set-shifting task.
It is widely accepted that chronic stress, which is considered a risk factor for several neuropsychiatric disorders, may have detrimental effects on prefrontal functions. In animal models, chronic stress produces morphol...
Effect of cocaine sensitization on alpha(1)-adrenoceptors in brain regions of the rat: an autoradiographic analysis.
We investigated the effects of repeated intermittent cocaine treatment, resulting in behavioral sensitization, on the density of alpha(1)-adrenoceptors in the rat brain measured by quantitative in vitro autoradiography o...
Neuroprotective potential of mGluR5 antagonist MTEP: effects on kainate-induced excitotoxicity in the rat hippocampus.
Extensive research into glutamate receptors in the central nervous system has shown important role of metabotropic glutamate receptors (mGluR) as potential targets for neuroprotective drugs. The aim of the present study...
Impact of the changes in P-glycoprotein activity on domperidone pharmacokinetics in rat plasma.
The effect of quinidine (QD) and grapefruit juice (GFJ) extract, P-glycoprotein inhibitors, on the domperidone (DOM) concentration in rat plasma was investigated. DOM, a dopamine D(2)-receptor antagonist is a substrate f...