Micropig as a reliable model for pharmacokinetic investigation of ceftriaxone. Cefepime, cefpirome and meropenem

The miniature pig is becoming a popular non-rodent animal model in biomedical research due to physiological similarities to humans, In addition, the micropig displays the advantages of large animal species for experimental pharmacokinetics. However, pharmacokinetics of antimicrobial agents are poorly documented in the pig and works are needed to establish interspecies comparisons. This prompted us to investigate the disposition of four well documented beta-lactams (ceftriaxone, cefepime, cefpirome and meropenem) in this model. Each of thr drug but ceftriaxone was given both by direct intravenous injection (or short infusion for meropenem) and continuous infusion. Blood samples were obtained over 0-12 h period using a catheter placed in the external jugular vein. All beta-lactams were assayed by h.p.l.c. In what concern ceftriaxone, marked differences appear between the micropig and man. The terminal half-life in the micropig was six to nine fold shorter than in human (1 h vs 6 to 9 h). 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 : 1.8 h, 1.8 h; pigs : 1.59 h, 1.44 h) as in the case for clearance values (human : 1.82, 1.80; pig : 1.97. 1.57 ml/min.kg(-1)) for cefepime and cefpirome respectively. The administration by continuous infusion do not appear to influence the elimination rate. Meropenem kinetics in the micropig were also similar to those in man. Furthermore, meropenem given by continuous infusion seems to br more quickly cleared than when given by short infusion. We concluded that the micropig is an adequate species for the study of the pharmacokinetics of cefepime, cefpirome and meropenem.