Clindamycin Pharmacokinetics in Loggerhead Sea Turtles from a Single IV, IM or Oral Dose
Clindamycin is a lincosamide antibiotic used to treat infections caused by gram-positive aerobic and anaerobic bacteria in multiple species. In monogastric mammalian species, clindamycin is well absorbed via all routes and has pharmacokinetic properties that support once- or twice- daily administration. It has been used to treat sea turtles with contaminated fractures and deep lacerations. However, lacking pharmacokinetic information in sea turtles, dosage regimens have been empirically derived or extrapolated from mammals. To determine the effectiveness of the current 5 mg/kg every 24 hours dosing regimen in achieving appropriate plasma concentrations of sufficient duration, a pharmacokinetic study was performed in loggerhead sea turtles (Caretta caretta). Pilot study results indicated that at a dose of 5 mg/kg, plasma concentrations of clindamycin were below the MIC of most bacteria soon after injection. Therefore, the clindamycin dose was increased to 10 mg/kg for a study in which three groups of eight juvenile loggerhead sea turtles (mean weight of 5 kg), housed at 30 °C at the National Marine Fisheries Service, Galveston Laboratory, received either a single IV, IM or oral dose of clindamycin. Blood was collected at various intervals to generate plasma concentration vs. time profiles and determine pharmacokinetic parameters. After IV administration, clearance was high and variable, and the plasma concentrations persisted above the MIC of 0.5 µg/mL for only 4 hours. The half-life also varied greatly among turtles with values ranging from 1 hour to over 50 hours. The volume of distribution was 5.4 L/kg (±5.2). Intramuscular administration yielded inconsistent absorption (average of 37%), a 1.2 (±0.4) hour half-life, and plasma concentrations above MIC of 0.5 µg/mL for only 2 hours. Oral clindamycin produced low concentrations that were insufficient to calculate pharmacokinetic values, although difficulties with administration (oral solution in squid mantles sutured shut and placed into the upper esophagus) may have contributed to the disappointing results for the oral route. These results indicate that because of rapid clearance, low oral absorption, and inconsistent IM absorption, clindamycin administration at 10 mg/kg every 24 hours does not achieve plasma concentrations at levels needed for effective therapy in sea turtles. Higher doses and more frequent administration should be considered to adequately treat gram-positive aerobic and anaerobic bacterial infections in sea turtles. The establishment of an appropriate dosing protocol for clindamycin in loggerhead sea turtles would improve the healthcare and speed the recovery of stranded loggerhead sea turtles.
We thank H. Fatzinger of the North Carolina Aquarium at Fort Fisher and B. Dorn of the North Carolina Aquarium at Pine Knoll Shores for facilitating the pilot studies, B. Higgins and D. Boon for logistical support in Galveston, and D. Dise for technical support analyzing the samples. For issuing permits to conduct this study, we thank M. Godfrey of the NC Wildlife Resources Commission, M. Koperski and R. Trindell of the Florida Fish and Wildlife Conservation Commission. We also thank Merck-Merial, Support Fund for Aquatic Animal Medicine, State of North Carolina, and Deborah Resnick for their financial support.