title: Pharmacokinetics of two spiroarsoranes administered intravenously or orally to rabbits.
abstract: 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.
authors.affiliation: Synthèse et Physicochimie Organique U A CNRS no. 471, Université Paul Sabatier, Toulouse, France.
authors.forename: L
authors.initials: L
authors.lastname: Rekik
authors.forename: Y
authors.initials: Y
authors.lastname: Coulais
authors.forename: M A
authors.initials: MA
authors.lastname: Rochas
authors.forename: G
authors.initials: G
authors.lastname: Campistron
authors.forename: J G
authors.initials: JG
authors.lastname: Wolf
authors.forename: G
authors.initials: G
authors.lastname: Houin
mesh_terms: 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
chemical_list: 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