Pharmacokinetic characteristics

The pharmacokinetic characteristics of osaterone acetate (17a-acetoxy -6-chloro-2- 94... 

Table 11.4 Some pharmacokinetic characteristics of short, intermediate and long-acting insulin preparations...

Step 4 Calculate individualized treatment regimen Determine treatment goals calculate dosage regimen based on pharmacokinetic characteristics of Ihe drug and the patients renal function... 

Benzodiazepinones such as 4 [14] have been claimed as PDE2 inhibitors, as have oxindoles related to 5 [15]. Compound 5 was reported to have an IC50 of 40 nM against PDE2. Preliminary ADME screening showed 5 to have the physicochemical and pharmacokinetic characteristics that should allow use as a tool to study PDE2 function in more detail [16]. 

At each of these stages, not only do the questions of interest change, but so also does the quality of the information available to answer these questions (Fig. 1 panel b). During target specification, all available pharmacokinetic characteristics are used to build a suitable model (e.g., disposition of the drug after administration of an immediate-release (IR) tablet, oral solution, or intravenous dose dose-proportionality time-dependence metabolism and pharmacological activity of metabolites efficiency of absorption from various sites etc.). However, since no formulations have yet been developed, the in vitro release behavior is unknown, as is the... 

Of the non-benzodiazepines that have been introduced recently for the treatment of anxiety and insomnia, buspirone and zopiclone have been the most extensively investigated so far. The pharmacokinetic characteristics of... 

By contrast, in the population approach, the raw data set that is analysed consists of concentration-time points (and other necessary data such as demographic information) taken from a large number (up to hundreds to thousands) of patients in Phase 11 and/or Phase 111 trials. The number of plasma samples per subject may be sparse but it is possible to estimate the individual pharmacokinetic characteristics of each subject and hence a measure of the mean parameters and their variability can be assessed. Relationships can be sought between patient characteristics (demographics, chnical status) and pharmacokinetic values is found, its consequence may be examined by looking for altered efficacy or safety which may not be possible in a traditional volunteer study. This might lead to demonstration of a therapeutic concentration range. 

There are many examples of drugs which are successful in the marketplace but which have less than optimal pharmacokinetics. However, when a compound which has desirable pharmacokinetic characteristics is selected for clinical development, it can lead to a smoother clinical development programme, fewer regulatory concerns, a more straightforward datasheet and,... 

Much remains to be done to improve the physicochemical properties and the pharmacokinetic characteristics of the estabhshed compound classes. A critical observer cannot help but wonder about the PK/PD profiles of many of the compoimds currently undergoing chnical development with hmited oral bioavailability, often necessitating intravenous administration, and rather short half fives in combination with often transient acetylation effects, the need for HDAC inhibitors with a more beneficial pharmacokinetic profile seems key. 

Elderly The pharmacokinetic characteristics of valganciclovir in elderly patients have not been established. Since elderly individuals frequently have a reduced glomerular filtration rate, pay particular attention to assessing renal function before and during administration of valganciclovir. 

Structural modifications needed to alter VD generally need to alter physicochemical properties (e.g., lipophilicity, charge, etc.) which in turn alter other pharmacokinetic characteristics of the molecule and may not be tolerated by the pharmacophore of the target. 

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