Pharmacokinetics of three new beta-lactams in the Yucatan micropig model administered by intravenous bolus injection and continuous infusion.
The miniature pig is becoming a popular non-rodent animal model in biochemical research because of physiological similarities to humans. In addition, the micropig presents the advantages of large animal species for experimental pharmacokinetics. However, pharmacokinetics of antimicrobial agents are poorly documented in the pig and further work is needed to establish interspecies comparisons. This prompted us to investigate the disposition of three well documented beta-lactams (cefepime, cefpirome and meropenem) in this model and also to evaluate the potential to use it for pharmacodynamic studies. Each drug was given following a single dose both by direct intravenous injection (or short infusion for meropenem) and continuous infusion. Six animals were enrolled in each group. Blood samples were obtained over a 0-12 h period, using a catheter placed in the external jugular vein. All beta-lactams were assayed by high performance liquid chromatography (HPLC). Pharmacokinetics of cefepime and cefpirome given by bolus injection in the microswine were close to those in man receiving equivalent dosage (i.e. 2 g). The terminal half-lives are similar (human: 1.80 h, 1.80 h; pig: 1.46 h, 1.29 h) as is the case for clearance values (human: 1.82, 1.80; pig: 1.90, 1.74 ml/min per kg) for cefepime and cefpirome, respectively. The administration by continuous infusion does not influence the elimination rate of cefepime, cefpirome and meropenem. Meropenem kinetics in the micropig were also similar to those in man. The terminal half-lives are similar (human, 0.83 h; pig, 0.88 h) as in the case for clearance values (human, 4.0 h; pig, 4.90 ml/min per kg) after 30 min intravenous infusion of meropenem. We concluded that the micropig is an adequate model for the study of the pharmacokinetics and probably the pertinent model for ex-vivo pharmacodynamics investigations of cefepime, cefpirome and meropenem.
Elkhaïli
H
H
Laboratoire de Pharmacocinétique de l'Institut de Bactériologie, 3 rue Koeberlé, 67 000 Strasbourg, France.
Levêque
D
D
Peter
J D
JD
Salmon
Y
Y
Salmon
J
J
Pompei
D
D
Monteil
H
H
Jehl
F
F