Naïve averaged, naïve pooled, and population pharmacokinetics of orally administered marbofloxacin in juvenile harbor seals.
OBJECTIVE
To determine the pharmacokinetics of marbofloxacin after oral administration in juvenile harbor seals (Phoca vitulina) at a dose of 5 mg/kg (2.3 mg/lb) and to compare pharmacokinetic variables after pharmacokinetic analysis by naïve averaged, naïve pooled, and nonlinear mixed-effects modeling.


METHODS
Original study. Animals-33 male and 22 female juvenile seals being treated for various conditions.


METHODS
Blood collection was limited to < or = 3 samples/seal. Plasma marbofloxacin concentrations were measured via high-pressure liquid chromatography with UV detection.


RESULTS
Mean +/- SE dose of marbofloxacin administered was 5.3 +/- 0.1 mg/kg (2.4 +/- 0.05 mg/lb). The terminal half-life, volume of distribution (per bioavailability), and clearance (per bioavailability) were approximately 5 hours, approximately 1.4 L/kg, and approximately 3 mL/min/kg, respectively (values varied slightly with the method of calculation). Maximum plasma concentration and area under the plasma-time concentration curve were approximately 3 microg/mL and 30 h x microg/mL, respectively. Naïve averaged and naïve pooled analysis appeared to yield a better fit to the population, but nonlinear mixed-effects modeling yielded a better fit for individual seals.


CONCLUSIONS
Values of pharmacokinetic variables were similar regardless of the analytic method used. Pharmacokinetic variability can be assessed with nonlinear mixed-effects modeling, but not with naïve averaged or naïve pooled analysis. Visual observation by experienced trainers revealed no adverse effects in treated seals. Plasma concentrations attained with a dosage of 5 mg/kg every 24 hours would be expected to be efficacious for treatment of infections caused by susceptible bacteria (excluding Pseudomonas aeruginosa).
KuKanich
Butch
B
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Huff
David
D
Riviere
Jim E
JE
Papich
Mark G
MG
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000662:veterinary; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D024841:Fluoroquinolones / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D046049:Phoca / Q000097:blood; D015363:Quinolones / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D015363:Quinolones; C080260:marbofloxacin