New approach for accurate simulation of human pharmacokinetics in an in vitro pharmacodynamic model: application to ciprofloxacin.
An in vitro pharmacodynamic model using a disposable dialyser unit and computer-controlled devices was developed. Feedback control of peristaltic pump flow rates is used to maintain constant flow rates, thus avoiding the problem of the modification of the physical properties of the tubing that generally occurs. Fast equilibrium is obtained with capillaries, which allows simulation of the same kinetic profile in the central and the peripheral compartments. Thus, more accurate simulation of plasma, extracapillary fluid or whole tissue kinetics can be performed. Our model was validated by simulation of a 30 min infusion of a 200 mg dose, and of an oral administration of a 500 mg dose of ciprofloxacin.
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Laboratoire de Pharmacocinétique et de Pharmacie Clinique, Faculté de Pharmacie, Université de Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux cedex, France. boubakar.ba@phcocin.u-bordeaux2.fr
Bernard
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Iliadis
A
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Quentin
C
C
Ducint
D
D
Etienne
R
R
Fourtillan
M
M
Maachi-Guillot
I
I
Saux
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MC
D000284:Administration, Oral; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics*; D003198:Computer Simulation; D003470:Culture Media; D006801:Humans; D007262:Infusions, Intravenous; D008954:Models, Biological
D000890:Anti-Infective Agents; D003470:Culture Media; D002939:Ciprofloxacin