Pharmacokinetics of sodium tungstate in rat and dog: a population approach.
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.
Le Lamer
S
S
Laboratoire de Pharmacocinétique Clinique, Faculté de Pharmacie, Montpellier, France.
Poucheret
P
P
Cros
G
G
de Richter
R K
RK
Bonnet
P A
PA
Bressolle
F
F
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001825:Body Fluid Compartments; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D014414:Tungsten / Q000097:blood; D017973:Tungsten Compounds / Q000493:pharmacokinetics*
D017973:Tungsten Compounds; C025399:sodium tungstate(VI); D014414:Tungsten