Pharmaceutical research
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Pharmaceutical research · Apr 2006
Pharmacokinetic consequences of active drug efflux at the blood-brain barrier.
The objective of this simulation study was to investigate how the nature, location, and capacity of the efflux processes in relation to the permeability properties influence brain concentrations. ⋯ Both poorly and highly permeable drugs can reach the same steady-state ratio, although the time to reach steady state will differ. The volume of distribution of unbound drug in the brain does not influence K(p,uu), but does influence the total brain-to-blood ratio K(p) and the time to reach steady state in the brain.
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Pharmaceutical research · Apr 2006
Use of in vitro critical inhibitory concentration, a novel approach to predict in vivo synergistic bactericidal effect of combined amikacin and piperacillin against Pseudomonas aeruginosa in a systemic rat infection model.
This study was undertaken to explore the use of in vitro critical inhibitory concentration (CIC) as a surrogate marker relating the pharmacokinetic (PK) parameters to in vivo bactericidal synergistic effect [pharmacodynamic (PD)] of amikacin + piperacillin combination against Pseudomonas aeruginosa in a systemic rat infection model. ⋯ The combination of amikacin and piperacillin exhibited synergistic killing effect on P. aeruginosa that could be modeled using CIC as a surrogate marker relating the PK parameters to in vivo bactericidal effect.