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.
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Pharmaceutical research · Aug 2005
Electrohydrodynamic comminution: a novel technique for the aerosolisation of plasmid DNA.
Naked plasmid DNA (pDNA) is a potential gene transfer agent for lung gene therapies but cannot be aerosolised without degradation using conventional nebulisation devices. This study investigated the viability of an alternative nebulisation technique, electrohydrodynamic (EHD) comminution for the aerosol delivery of naked DNA in vivo. ⋯ This study demonstrates for the first time that respirable aerosols of naked pDNA can be generated without plasmid degradation and that EHD comminution is an appropriate technique for the aerosolisation of delicate gene transfer agents.
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Pharmaceutical research · Apr 2005
Method validation and measurement of biomarkers in nonclinical and clinical samples in drug development: a conference report.
Biomarkers are increasingly used in drug development to aid scientific and clinical decisions regarding the progress of candidate and marketed therapeutics. Biomarkers can improve the understanding of diseases as well as therapeutic and off-target effects of drugs. Early implementation of biomarker strategies thus promises to reduce costs and time-to-market as drugs proceed through increasingly costly and complex clinical development programs. ⋯ This summary report of the workshop focuses on the major issues discussed during presentations and open forums and noted consensus achieved among the participants on topics from nomenclature to best practices. For example, it was agreed that because reliable and accurate data provide the basis for sound decision making, biomarker assays must be validated in a manner that enables the creation of such data. The nature of biomarker measurements often precludes direct application of regulatory guidelines established for clinical diagnostics or drug bioanalysis, and future guidance on biomarker assay validation should therefore be adaptable enough that validation criteria do not stifle creative biomarker solutions.