Clindamycin is a lincosamide antibiotic that is 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 assess current empiric dose recommendations (5 mg/kg q 24 h; 2.5–5 mg/kg kg q 12–24 h) 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 a minimum inhibitory concentration of 0.5 μg/ml 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 with a median weight of 5.03 kg housed at 30°C received a single intravenous, intramuscular, or oral dose of clindamycin. Blood was collected at various intervals to generate plasma concentration vs. time profiles. Noncompartmental analysis was used to determine pharmacokinetic parameters. After IV administration, clearance was high and variable, and the plasma concentrations persisted above 0.5 μg/ml for only 4 hr. The half-life also varied considerably among turtles, with values ranging from 1 to >50 h because of persistent low concentrations in five of the turtles. The median volume of distribution at steady state was 4.5 L/kg. Intramuscular administration yielded inconsistent absorption (median F = 45%), a 1.0-h median half-life, and plasma concentrations above 0.5 μg/ml for <4 h. Oral clindamycin produced low concentrations that were insufficient to calculate pharmacokinetic values, although administration technique (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, clindamycin administration at 10 mg/kg q 24 h does not achieve plasma concentrations needed for effective therapy in loggerhead sea turtles. Higher doses and more frequent administration should be considered to treat anaerobic and Gram-positive aerobic bacterial infections effectively in sea turtles.
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1 December 2011
Pharmacokinetics of Clindamycin in Loggerhead Sea Turtles (Caretta caretta) after a Single Intravenous, Intramuscular, or Oral Dose
Craig A. Harms,
Elizabeth A. Cranston,
Mark G. Papich,
Mauricio X. Rodriguez,
Benjamin M. Higgins,
Joseph P. Flanagan
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Caretta caretta
clindamycin
loggerhead sea turtle
pharmacokinetics