Biopharmaceutics and pharmacokinetics of 5-phenyl-1, 2-dithiole-3-thione complexed with sulfobutyl ether-7-beta-cyclodextrin in rabbits.
The biopharmaceutics and pharmacokinetics of 5-phenyl-1, 2-dithiole-3-thione (5PDTT) were investigated in rabbits, after administration as a complex with sulfobutyl-ether-7-beta-cyclodextrin (SBE7-beta-CD) by intravenous and oral routes and as a micronized powder by oral route. 5PDTT had a rapid and large red blood cell partitioning that was not dependent on drug concentration either in vitro or ex vivo. The blood clearance was very high (354 +/- 131 mL/min) suggesting extrahepatic metabolism and/or nonrenal elimination and a significant volume of distribution (67 +/- 76 L). The renal clearance was 0.17% of total clearance. 5-phenyl-1,2-dithiol-3-one (5PDTO) was identified as a metabolite in blood and urine. The bioavailability of 5PDTT following administration of 5PDTT/SBE7-beta-CD complex was estimated to 41% while it was close to zero when 5PDTT was given as a micronized powder.
Lefeuvre
C
C
Laboratoire de Pharmacie Galénique, Biopharmacie et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, 35043 Rennes Cedex, France.
Le Corre
P
P
Dollo
G
G
Chevanne
F
F
Burgot
J L
JL
Le Verge
R
R
D000284:Administration, Oral; D000465:Algorithms; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001702:Biopharmaceutics; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry; D004912:Erythrocytes / Q000187:drug effects; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D011817:Rabbits; D012995:Solubility; D013871:Thiones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013876:Thiophenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D047392:beta-Cyclodextrins
C401802:5-phenyl-1,2-dithiole-3-thione; D016588:Anticarcinogenic Agents; D003505:Cyclodextrins; C103513:SBE7-beta-cyclodextrin; D013871:Thiones; D013876:Thiophenes; D047392:beta-Cyclodextrins