Vol. 294, Issue 2, 714-721, August 2000

Pharmacokinetics of Sodium Tungstate in Rat and Dog: A Population Approach

Sophie Le Lamer, Patrick Poucheret, Gérard Cros, Renaud Kiesgen de Richter, Pierre-Antoine Bonnet and Françoise Bressolle

Laboratoire de Pharmacocinétique Clinique (S.L.L., F.B.) and Laboratoire de Pharmacologie (P.P., G.C.), Faculté de Pharmacie, Montpellier, France; and Agence Française de Sécurité Sanitaire des Produits de Santé (R.K.d.R., P.-A.B.), Vendargues, France

Sodium tungstate has been found to correct hyperglycemia in insulin- and noninsulin-dependent models of diabetes when administered in drinking fluid with a low degree of toxicity; thus, it provides a potential treatment for diabetes. In the present report, pharmacokinetic studies with sodium tungstate were carried out in the Sprague-Dawley rat and beagle dog. This drug was administered either i.v. (8.97 mg/kg in rat; 25 and 50 mg/kg in dog) or orally in the form of solution (35.9 and 107.7 mg/kg in rat; 25 and 50 mg/kg in dog). Tungsten was quantified using an inductively coupled plasma method. Pharmacokinetic parameters were estimated using a population approach. Sodium tungstate followed first order kinetics, and plasma concentration-versus-time data were adequately described by a two-compartment model. In rat, bioavailability was high (92%), whereas it was lower in dog (approximately 65%). The total volume of distribution expressed by unit of body weight was much higher when the animal was smaller (0.46 l/kg in rat versus 0.23 l/kg in dog). The total body clearance normalized by weight, 0.19 l/h/kg in rat versus 0.043 l/h/kg in dog, changed as for the volume of distribution. The elimination half-life was two times higher in dog (approximately 4 h) than in rat (approximately 1.7 h). In the range of 35.9 to 107.7 mg/kg after oral administration in rat and 25 to 50 mg/kg after oral and i.v. administration in dog, tungsten plasma concentrations increased in proportion to dose.