Pharmacokinetics of two spiroarsoranes administered intravenously or orally to rabbits.
The pharmacokinetics of two spiroarsorane molecules (1,2) were investigated after both intravenous bolus and an oral administration in rabbits. After iv administration of a 15-mg/kg dose, for the two substances, the plasma concentration-time curves were well described by an open two-compartmental model. The half-lives of the first phase were 0.47 +/- 0.12 and 0.27 +/- 0.02 h for 1 and 2, respectively. The half-lives of the terminal phase were of the same order of magnitude for the two substances: 4.38 +/- 0.24 and 6.03 +/- 1.14 h, respectively. Total plasma clearances were 2.47 +/- 0.44 and 0.81 +/- 0.04 L/h, respectively, and the steady-state volume of distribution of 2 (14.99 +/- 2.57 L) was larger than that of 1 (4.27 +/- 0.28 L). After oral administration, spiroarsorane 2 was not absorbed. The availability of the suspension of 1 was 18%. The rate of the absorption phase of 1 showed a saturation process, probably due to the solubility of the molecule. When increasing oral doses of 1 (15, 30, and 60 mg/kg) were administered, the plasma concentrations did not increase to the same extent.
Rekik
L
L
Synthèse et Physicochimie Organique U A CNRS no. 471, Université Paul Sabatier, Toulouse, France.
Coulais
Y
Y
Rochas
M A
MA
Campistron
G
G
Wolf
J G
JG
Houin
G
G
D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D001147:Arsanilic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000652:urine; D001152:Arsenicals / Q000493:pharmacokinetics*; D005369:Filaricides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D007275:Injections, Intravenous; D011817:Rabbits; D013141:Spiro Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine
D000871:Anthelmintics; D000935:Antifungal Agents; D001152:Arsenicals; D005369:Filaricides; D013141:Spiro Compounds; D014344:Trypanocidal Agents; C059854:octamethyl-2,2,3,3,7,7,8,8-arsa-5-anilino-5-spiro-(4,4)-nonane; C059856:octamethyl-2,2,3,3,7,7,8,8-arsa-5-(4-hydroxy)-3-acetamidophenyl-5-spiro-(4,4)-nonane; D001147:Arsanilic Acid