Ketorolac is a nonsteroidal anti‐inflammatory drug that possesses potent analgesic activity comparable to morphine. The opioid shortage in the United States has led to an unreliable supply of opioids for use in rehabilitation facilities, thus underscoring the need for research on the safe and effective use of nonopioid alternatives. The goal of this study was to determine the pharmacokinetics of ketorolac after a single 0.25 mg/kg intramuscular injection administered to injured Eastern box turtles (Terrapene carolina carolina). A sparse blood sampling protocol was used to collect samples from 32 wild turtles that presented to the Turtle Rescue Team at North Carolina State University for traumatic injuries. Blood was collected from 0 to 24 hr after injection and analyzed via high‐pressure liquid chromatography (HPLC). A nonlinear mixed‐effects (NLME) model was fitted to the data to obtain typical values for population parameters. Using this approach, we identified a long half‐life (T1/2) of 9.78 hr and a volume of distribution (Vss) of 0.26 L/kg. We have concluded that this long T1/2 for a dose of 0.25 mg/kg ketorolac‐injected IM provides plasma levels above a previously published target level for 24‐hour analgesia to allow for once daily dosing.
Ceftazidime, a third-generation cephalosporin, is important for treating opportunistic bacterial infections in turtles. Antibacterial dosage regimens are not well established for wild turtles and are often extrapolated from other reptiles or mammals. This investigation used a population pharmacokinetic approach to study ceftazidime in wild turtles presented for rehabilitation. Ceftazidime was administered to 24 wild turtles presented to the Turtle Rescue Team at North Carolina State University. A sparse blood sampling protocol was used to collect samples from 0 to 120 hr with three samples per individual after injection. Plasma samples were analyzed by high-pressure liquid chromatography (HPLC). A nonlinear mixed-effects model (NLME) was fitted to the data to determine typical values for population parameters. We identified a long half-life (T½) of approximately 35 hr and volume of distribution (V ) of 0.26 L/kg. We concluded that this long T½ will allow for a dose of 20 mg/kg injected IM to maintain concentrations above the MIC of most wild-type bacteria for 5 days. Because of long intervals between injections, stability of stored formulations was measured and showed that 90% strength was maintained for 120 hr when stored in the refrigerator and for 25 days when stored in the freezer.
Blockade of potassium channels with 4-aminopryidine (4-AP) restores conduction to demyelinated axons and improves function. Unfortunately, 4-AP causes adverse effects and its clinical effects are unpredictable and limited. Derivatives of 4-AP have been tested in models of spinal cord injury in guinea pigs; three derivatives (methyl-, ethyl- and t-butyl carbamate derivatives) showed promise. This study investigates the safety and pharmacokinetics of these derivatives in dogs. Each derivative was administered orally to dogs starting at doses below effective doses in guinea pigs, and increasing the dose on sequential days. Routine blood work was performed prior to and 24 h after drug administration, blood samples were collected at intervals over 24 h after drug administration, and dogs were monitored for side effects. Derivative plasma levels were determined using high-pressure liquid chromatography. Cerebrospinal fluid (CSF) samples were taken to determine CSF levels. No adverse effects were seen even when using doses higher than those that improved conduction in spinal cord injured guinea pigs. Peak plasma levels occurred at 36.6 (ethyl), 87 (t-butyl) and 175 (methyl) min and plasma level was related to drug dose. Penetration of the central nervous system (CNS) was good, with CSF levels higher than plasma levels for the t-butyl derivative.
An adult male eastern box turtle presented to the Turtle Rescue Team at North Carolina State University with clinical signs of an upper respiratory tract infection. After unsuccessful treatment with broad spectrum antibiotics, multidrug-resistant Escherichia coli was cultured from the infection that was resistant to commonly used antimicrobial agents. Based on the culture and susceptibility testing, 10 mg/kg of meropenem was administered intramuscularly every 24 hours for seven days. Meropenem plasma concentrations were measured to ensure that an optimum antibiotic dose was administered. Following treatment with meropenem, clinical signs ceased and subsequent culture reports were negative. Meropenem plasma concentrations identified a short half-life (4.17 hours) necessitating once-daily dosing to maintain effective concentrations. Because multiple doses were delivered from a single administration vial, the strength of reconstituted vials of meropenem during storage in the refrigerator was tested. The meropenem concentration was maintained above 90 per cent for 48 hours.
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