Plasma and Tissue Concentrations of Itraconazole in the Kemp's Ridley Sea Turtle (Lepidochelys kempi)
Charles A. Manire1; Howard L. Rhinehart1; Gennethel J.
Pennick2; Michael G. Rinaldi2
Abstract
Few pharmacokinetic studies have been carried out in reptiles and there
are no published studies regarding the use of itraconazole in turtles. Such a lack of
information makes treatment of stranded sea turtles, either prophylactically or for resistant
fungal infections, challenging. Plasma samples were collected from a group of six juvenile
Kemp's Ridley sea turtles, Lepidochelys kempi, being treated for complications arising
from hypothermia at the Sea Turtle Rehabilitation Hospital in Sarasota, Florida. In addition,
tissue samples were collected when one of the turtles undergoing treatment died. The turtles
were being treated with itraconazole, either in the capsular form or as the oral solution, and
were treated at several dosage levels. Following removal from all drugs, two of the turtles
additionally were given a single dose of 10 mg/kg of the oral solution and plasma samples were
collected at time intervals following the dose. Plasma itraconazole and hydroxyitraconazole
(major bioactive metabolite) concentrations were determined using a modified and validated
reverse-phase high-performance liquid chromatography technique. The results of this study
indicate that peak plasma concentrations of itraconazole are reached in 4-8 hr and peak plasma
concentrations of hydroxyitraconazole are reached in 24-48 hr following a single dose of the
oral solution. Elimination half-life of plasma itraconazole was 38 and 65 hr for two turtles
under study while the half-life of hydroxyitraconazole was 69 and 77 hr, respectively. Tissue
concentrations in the turtle that died were adequate for inhibition of susceptible fungi as
determined by bio-assay. This study would suggest that an effective oral itraconazole dosage for
sea turtles would be 5-10 mg/kg given every 3 days.