Vanadium pharmacokinetics and oral bioavailability upon single-dose administration of vanadyl sulfate to rats.
Vanadium pharmacokinetic parameters and oral bioavailability were determined after administration of vanadyl sulfate, an antidiabetic agent, to male Wistar rats. An optimal sampling design was used over a 21-day period; vanadium was measured in blood by atomic absorption spectrophotometry (AAS). After i.v. bolus injection (3.025 mg V/kg body weight), a three-compartment model was fitted to the data. Mean (+/- SD) half-lives were 0.90 +/- 0.56 hours, 24.8 +/- 14.5 h and 201 +/- 74 h, respectively, for the three phases observed. Vanadium clearance averaged 37.6 +/- 15.8 mL/h. Initial volume of distribution was 2.43 +/- 1.22 L/kg whereas total volume of distribution was 25.4 +/- 3.9 L/kg; these values largely exceeded body weight (i.e. 300 g), in agreement with a great uptake and retention of vanadium in tissues. After oral gavage administration (15.12 and 7.56 mg V/kg body weight), vanadium disposition was best described by a three-compartment model, with absorption appearing to occur by a zero-order rate. This process lasted 10.3 +/- 1.3 h and 10.9 +/- 1.1 h for the two dosage levels, respectively. Half-lives corresponding to the terminal log-linear part of the curve were 173.5 +/- 1.6 h and 172 +/- 6 h (Bayesian estimates). No dose-dependency was observed for any of the parameters determined. Absolute bioavailabilities, with reference to the i.v. administration, were 12.5% and 16.8% when determined from AUCmod. Bioavailability appeared to be higher than generally stated in the literature.
Azay
J
J
EA2987: Laboratoire de Pharmacologie et Physiopathologie Expérimentales, Faculté de Pharmacie, 34093 Montpellier Cedex 5, France.
Brès
J
J
Krosniak
M
M
Teissedre
P L
PL
Cabanis
J C
JC
Serrano
J J
JJ
Cros
G
G
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013054:Spectrophotometry, Atomic; D017968:Vanadium Compounds / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
D007004:Hypoglycemic Agents; D017968:Vanadium Compounds; C034028:vanadyl sulfate