Population pharmacokinetics of ceftazidime after a single intramuscular injection in wild turtles.

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 (VSS ) 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.

Pharmacokinetics of 4-aminopyridine derivatives in dogs.

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.