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.
Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Św Marii Magdaleny 14, PL 61-861 Poznań, Poland. agnbienert@op.pl
Agnieszka
A
Bienert
Agnieszka
A
Kamińska
Jan
J
Olszewski
Joanna
J
Gracz
Tomasz
T
Grabowski
Anna
A
Wolc
Edmund
E
Grześkowiak
D000082:Acetaminophen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000496:Alloxan; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D005123:Eye / Q000378:metabolism*; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D011817:Rabbits; D014018:Tissue Distribution
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D000496:Alloxan; C037386:acetaminophen glucuronide