Influence of food and diabetes on pharmacokinetics of sodium tungstate in rat.
In this paper, the influence of food and diabetes on the pharmacokinetics of sodium tungstate in rat was investigated. The compound was administered intravenously (9 mg/kg) and orally in the form of solution (36 mg/kg). An empirical Bayes methodology was used to compute individual pharmacokinetic parameters. Sodium tungstate followed first-order kinetics, and plasma concentration versus time data were described by a two-compartment model. A significant relationship was found between the bioavailability and the status of the animals. Total plasma clearance and elimination half-life averaged 3.1 ml/min/kg and 1.6 h, respectively. Food had some effects on the extent of sodium tungstate absorption. After oral administration, the bioavailability (0.67 versus 0.85), C(max) (6.10 versus 15.2 microg/ml) and AUC (70.7 versus 105 mgh/l) were 20, 60 and 32% lower in fed than in fasted rats, respectively. The presence of cellulose and sulphate anions in rat chow could partially explain the fed state-associated reduction of tungstate bioavailability. In streptozotocin-induced diabetic fed rats, a 25% decrease occurred in AUC and F, and a 14% increase occurred in the elimination rate constant compared with healthy fed rats. These changes could be explain on the one hand, by the increase of liquid consumption and food intake, and on the other hand, by a gastroparesis in the early diabetic rats.
Le Lamer-Déchamps
S
S
Clinical Pharmacokinetic Laboratory, Faculty of Pharmacy, 34093 Montpellier Cedex 5, France.
Poucheret
P
P
Cros
G
G
Bressolle
F
F
D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D018565:Food-Drug Interactions / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017973:Tungsten Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D017973:Tungsten Compounds; C025399:sodium tungstate(VI)