In vivo simulation of human pharmacokinetics in the rabbit |
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Authors: | Denis Bugnon Gilles Potel Jocelyne Caillon Denis Baron Henri B Drugeon Philippe Feigel Marie F Kergueris |
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Institution: | (1) Laboratoire d’Antibiologie Clinique et Expérimentale, Faculté de Médecine de Nantes, 1 rue Gaston Veil, 44035 Nantes, France;(2) Service de Réanimation, Centre Hospitalier Départemental Les Oudairies, 85025 La Roche sur Yon Cedex, France;(3) Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Nantes, 1 place Alexis Ricordeau, 44000 Nantes, France |
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Abstract: | The evaluation of drugs in vivo is often based on experimental models using small animals such as mice, rats and rabbits. However, these models could be
improved to correspond more closely to the human situation if the pharmacokinetics of the drugs tested in animals were similar
to that observed in humans. The use of a computer-controlled pump allowing an adequate flow of tobramycin and amikacin to
be infused into rabbits enabled us to simulate the human pharmacokinetics of these antibiotics in vivo in this study. The function defining the rate of infusion required to perform the simulation of an intravenous bolus was
first determined generally and symbolically for linear pharmacokinetic models independently from the number of compartments
involved. The practical simulation of a decreasing monoexponential serum profile with a half-life of 2 h (one-compartment
model for the human pharmacokinetics of aminoglycosides) was then studied for tobramycin and amikacin on the basis of a two-compartment
model in the animal. The kinetics obtained had an apparent elimination half-life of 1.97 and 1.86 h, respectively. Linearity
of the semilogarithmic regressions of the profiles obtained was quite sound. Finally, an a posteriori analysis of the pharmacokinetic model and its parameters is proposed on the basis of the results obtained after simulation. |
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