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THE PIGLET AS A MODEL FOR CEFONICID PHARMACOKINETICS

The piglet is a useful pharmacodynamic model for the study of catecholamines and an acceptable pharmacokinetic (PK) model for methylxanthines. We evaluated the piglet as a model for the PK of cefonicid, a second generation cephalosporin. Cefonicid (C) PK were evaluated in 13 piglets at 3 (n=6) and 6 (n=7) days of age. Following a single I.V. dose of 50 mg/kg, blood samples (n=10) were obtained over 24 hr. Serum ultrafiltrate was prepared for determination of unbound C by membrane centrifugation, and C was quantitated by HPLC (LLD = 5 mg/L; C.V. <10%). ESTRIP was used to generate polyexponential parameter estimates necessary for PK calculations. No significant differences were found between the 3 and 6 day old animals with respect to T½ (1.4±0.1 vs. 1.04±0.07 hr), total clearance (CL; 0.39±0.03 vs. 0.31±0.07 L/hr/kg) or Vd(area) (0.3±0.04 vs. 0.28±0.06 L/kg). The PK parameters for C in the piglets were markedly different from those in young adult humans (T½=4.8 hr; Vd=0.12 L/kg), as was true for the free fraction of C from piglets (93.0%) vs. healthy adults (3.1%). Comparison of piglet serum to that from human neonates revealed a significant difference in the albumin concentration (1.5±0.2 gm% for piglet vs. 4.3±0.2 gm% for human) and the total protein:albumin ratio (2.7±0.3 for piglet vs. 1.5± 0.1 for human). The markedly increased CL of C in the piglet may be consequent to interspecies differences in C protein binding. Our data suggest that the piglet may not be an adequate model to evaluate the PK of C for extrapolation to the human infant.