MICROPIG AS A RELIABLE MODEL FOR PHARMACO KINETIC INVESTIGATION OF CEFTRIAXONE - CEFEPIME, CEFPIROME AND MEROPENEM

The miniature pig is becoming a popular non-rodent animal model in bio medical research due to physiological similarities to humans, In addit ion, the micropig displays the advantages of large animal species for experimental pharmacokinetics. However, pharmacokinetics of antimicrob ial agents are poorly documented in the pig and works are needed to es tablish interspecies comparisons. This prompted us to investigate the disposition of four well documented beta-lactams (ceftriaxone, cefepim e, cefpirome and meropenem) in this model. Each of thr drug but ceftri axone was given both by direct intravenous injection (or short infusio n for meropenem) and continuous infusion. Blood samples were obtained over 0-12 h period using a catheter placed in the external jugular vei n. All beta-lactams were assayed by h.p.l.c. In what concern ceftriaxo ne, marked differences appear between the micropig and man. The termin al half-life in the micropig was six to nine fold shorter than in huma n (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 receiv ing 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 clear ance values (human : 1.82, 1.80; pig : 1.97. 1.57 ml/min.kg(-1)) for c efepime and cefpirome respectively. The administration by continuous i nfusion do not appear to influence the elimination rate. Meropenem kin etics in the micropig were also similar to those in man. Furthermore, meropenem given by continuous infusion seems to br more quickly cleare d 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.