title: Steady-state plasma concentrations of itraconazole after oral administration in Kemp's ridley sea turtles, Lepidochelys kempi.
abstract: Pharmacokinetic studies of antifungal agents in reptiles are uncommon. Itraconazole, which has been used prophylactically in juvenile sea turtles suffering from hypothermia (cold stunning) on a regular basis, was evaluated for steady-state plasma concentrations. Five Kemp's ridley sea turtles (Lepidochelys kempi) receiving itraconazole at several dosages in a rehabilitation program had blood collected within 24 hr to estimate dosing frequency. Subsequently, serial blood samples of Kemp's ridley sea turtles that were given itraconazole at several dosages for 30 days to treat cold stunning were collected at various intervals to evaluate itraconazole plasma concentrations. Tissue samples were collected from one Kemp's ridley that died during rehabilitation. Plasma concentrations of itraconazole (and of hydroxyitraconazole [OH-ITRA], one of its major bioactive metabolites) were determined using a modified, validated reverse-phase high-performance liquid chromatography technique. Itraconazole concentrations in tissues were determined by bioassay to be far greater than the plasma concentrations measured in any of the turtles. At a 15-mg/kg dosage, the half-life (t1/2) was 75 hr for itraconazole and 55 hr for OH-ITRA. All dosages produced adequate concentrations in some turtles, but consistent therapeutic concentrations were produced only at 15 mg/kg q72hr and 5 mg/kg s.i.d., with the latter producing the highest plasma concentrations.
authors.affiliation: Sea Turtle Rehabilitation Hospital, Mote Marine Laboratory and Aquarium, 1600 Ken Thompson Parkway, Sarasota, Florida 34236, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Manire
authors.forename: Howard L
authors.initials: HL
authors.lastname: Rhinehart
authors.forename: Gennethel J
authors.initials: GJ
authors.lastname: Pennick
authors.forename: Deanna A
authors.initials: DA
authors.lastname: Sutton
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hunter
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rinaldi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000835:Animals, Wild; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000662:veterinary; D007035:Hypothermia / Q000150:complications / Q000662:veterinary; D017964:Itraconazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014426:Turtles / Q000097:blood*
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole